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Zhang S, Lu X, Chen J, Xiong S, Cui Y, Wang S, Yue C, Han Q, Yang B. Promotion of angiogenesis and suppression of inflammatory response in skin wound healing using exosome-loaded collagen sponge. Front Immunol 2024; 15:1511526. [PMID: 39669582 PMCID: PMC11634875 DOI: 10.3389/fimmu.2024.1511526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 11/13/2024] [Indexed: 12/14/2024] Open
Abstract
Effectively promoting skin wound healing remains a significant challenge in the medical field. Although stem cell-derived exosomes show potential in tissue regeneration, their local delivery and sustained release face challenges. To address these issues, we developed a collagen sponge based on type I and recombinant humanized type III collagen. Our study confirmed that exosomes were successfully loaded onto the sponge (sponge-Exo) and the sponge-Exo gradually released exosomes into the local milieu. The sponge-Exo played a crucial role in promoting the transition of macrophages from an inflammatory M1 phenotype to a regenerative M2 phenotype. Moreover, it enhanced the migration and proliferation of HDFs and promoted angiogenesis in HUVECs. Additionally, our findings revealed that the sponge-Exo accelerated wound healing by suppressing inflammatory response and stimulating angiogenesis in a rat full-thickness skin wounds model. Next generation sequencing (NGS) was used to explore the underlying mechanism of wound healing, and the results showed that the miRNAs (hsa-miR-21-5p and hsa-miR-29a-5p) associated with wound healing in exosomes were significantly up-regulated. These results highlight the remarkable effects of sponge-Exo on macrophage transformation, cell migration, proliferation and angiogenesis, which provide a potential prospect for the application in the field of skin wound healing.
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Affiliation(s)
- Siqi Zhang
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu, China
| | - Xugang Lu
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu, China
| | - Jun Chen
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu, China
| | - Shibing Xiong
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu, China
| | - Yifan Cui
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu, China
| | - Simeng Wang
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu, China
| | - Chongxia Yue
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu, China
- NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterial & Institute of Regulatory Science for Medical Devices & NMPA Research Base of Regulatory Science for Medical Devices, Sichuan University, Chengdu, China
| | - Qianqian Han
- Medical Device Testing Institute, National Institutes for Food and Drug Control, Beijing, China
| | - Bangcheng Yang
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu, China
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Yang N, Shen R, Yang W, Zhang S, Gong T, Liu Y. Biomimetic pulp scaffolds prepared from extracellular matrix derived from stem cells from human exfoliated deciduous teeth promote pulp-dentine complex regeneration. Int Endod J 2024; 57:1279-1292. [PMID: 38828966 DOI: 10.1111/iej.14099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 03/25/2024] [Accepted: 05/08/2024] [Indexed: 06/05/2024]
Abstract
AIM To evaluate the role of biomimetic pulp scaffolds derived from the extracellular matrix derived of stem cells from human exfoliated deciduous teeth (SHED-ECM-PS) in promoting pulp-dentine complex regeneration. METHODOLOGY SHED-ECM-PS was prepared through cell aggregation and decellularization techniques. Histological and immunofluorescence analyses, scanning electron microscopy, and DNA quantification assays were used to characterize the SHED-ECM-PS. Additionally, a tooth slice implantation model was established to evaluate the effects of SHED-ECM-PS on regeneration of the pulp-dentine complex in vivo. Extraction medium for SHED-ECM-PS was prepared, and its effect on bone marrow mesenchymal stem cells (BMMSCs) was assessed in vitro. Cell counting kit-8 and Ki-67 staining assays were performed to determine cell proliferation. The rate of apoptosis was evaluated by flow cytometry. Wound healing and transwell assays were conducted to evaluate cell migration. Alizarin red S staining was performed to examine mineralized nodule formation. Western blotting was used to detect the expression of osteogenic and odontogenic markers. The results were analysed using an independent two-tailed Student's t-test. p < .05 was considered statistically significant. RESULTS SHED-ECM-PS was successfully constructed, exhibiting a striped dental pulp-like shape devoid of nuclear structures or DNA components, and rich in fibronectin, collagen I, DMP1 and DSPP. Notably, SHED-ECM-PS showed no impact on the proliferation or apoptosis of BMMSCs. Histological analysis revealed that dental pulp fibroblasts formed an interwoven mesh in the root canal, and angiogenesis was observed in the SHED-ECM-PS group. Moreover, a continuous, newly formed tubular dentine layer with polarized odontoblast-like cells was observed along the inner wall of the root canal. SHED-ECM-PS promoted the migration, polar alignment and mineralized nodule formation of BMMSCs and specifically elevated the expression levels of odontogenic markers, but not osteogenic markers, compared with the control group in vitro. CONCLUSION SHED-ECM-PS exhibited no cytotoxicity and promoted pulp-dentine complex regeneration in vivo as well as cell migration and odontogenic differentiation of BMMSCs in vitro. These findings provide evidence that SHED-ECM-PS, as a novel biological scaffold, has the potential to improve the outcomes of REPs.
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Affiliation(s)
- Ning Yang
- Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, China
- Liaoning Province Key Laboratory of Oral Disease, Shenyang, China
| | - Rou Shen
- Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, China
- Liaoning Province Key Laboratory of Oral Disease, Shenyang, China
| | - Wenxiao Yang
- Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, China
- Liaoning Province Key Laboratory of Oral Disease, Shenyang, China
| | - Shengcai Zhang
- Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, China
- Liaoning Province Key Laboratory of Oral Disease, Shenyang, China
| | - Tianxing Gong
- Department of Biomedical Engineering, Shenyang University of Technology, Shenyang, China
| | - Yao Liu
- Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, China
- Liaoning Province Key Laboratory of Oral Disease, Shenyang, China
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Li J, Sun J, Xu M, Yang L, Yang N, Deng J, Ma Y, Qi Y, Liu Z, Ruan Q, Liu Y, Huang Y. Human cytomegalovirus infection impairs neural differentiation via repressing sterol regulatory element binding protein 2-mediated cholesterol biosynthesis. Cell Mol Life Sci 2024; 81:289. [PMID: 38970696 PMCID: PMC11335213 DOI: 10.1007/s00018-024-05278-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 05/11/2024] [Accepted: 05/13/2024] [Indexed: 07/08/2024]
Abstract
Congenital human cytomegalovirus (HCMV) infection is a major cause of abnormalities and disorders in the central nervous system (CNS) and/or the peripheral nervous system (PNS). However, the complete pathogenesis of neural differentiation disorders caused by HCMV infection remains to be fully elucidated. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells (MSCs) with a high proliferation and neurogenic differentiation capacity. Since SHEDs originate from the neural crest of the early embryonic ectoderm, SHEDs were hypothesized to serve as a promising cell line for investigating the pathogenesis of neural differentiation disorders in the PNS caused by congenital HCMV infection. In this work, SHEDs were demonstrated to be fully permissive to HCMV infection and the virus was able to complete its life cycle in SHEDs. Under neurogenic inductive conditions, HCMV infection of SHEDs caused an abnormal neural morphology. The expression of stem/neural cell markers was also disturbed by HCMV infection. The impairment of neural differentiation was mainly due to a reduction of intracellular cholesterol levels caused by HCMV infection. Sterol regulatory element binding protein-2 (SREBP2) is a critical transcription regulator that guides cholesterol synthesis. HCMV infection was shown to hinder the migration of SREBP2 into nucleus and resulted in perinuclear aggregations of SREBP2 during neural differentiation. Our findings provide new insights into the prevention and treatment of nervous system diseases caused by congenital HCMV infection.
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Affiliation(s)
- Jianming Li
- Virology Laboratory, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Jingxuan Sun
- Virology Laboratory, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Mingyi Xu
- Virology Laboratory, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Lei Yang
- Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, China
- Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, Liaoning, China
| | - Ning Yang
- Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, China
- Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, Liaoning, China
| | - Jingui Deng
- Virology Laboratory, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Department of Microorganism Laboratory, Shenyang Center for Disease Control and Prevention, Shenyang, Liaoning, China
| | - Yanping Ma
- Virology Laboratory, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Departments of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Ying Qi
- Virology Laboratory, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Departments of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Zhongyang Liu
- Virology Laboratory, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Departments of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Qiang Ruan
- Virology Laboratory, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
- Departments of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
| | - Yao Liu
- Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, China.
- Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, Liaoning, China.
| | - Yujing Huang
- Virology Laboratory, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
- Departments of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
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Pawar M, Rathi N, Kharat A, Bhonde R, Patole VC. Role of the Stem Cells from Human Deciduous Teeth in Dentistry: A Review. JOURNAL OF PHARMACY AND BIOALLIED SCIENCES 2024; 16:S1974-S1976. [PMID: 39346474 PMCID: PMC11426779 DOI: 10.4103/jpbs.jpbs_630_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 06/10/2024] [Accepted: 06/16/2024] [Indexed: 10/01/2024] Open
Abstract
Stem cells isolated from human exfoliated deciduous teeth or SHED possess high rate of proliferation along with high osteogenic as well as neurogenic differentiation when compared with dental pulpal stem cells. This stem cell population is an important source for therapeutic regeneration of tissues. Hence, the aim of present review article was to analyze the potential applications of SHED.
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Affiliation(s)
- Madhura Pawar
- Department of Pedodontics and Preventive Dentistry, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra, India
| | - Nilesh Rathi
- Department of Pedodontics and Preventive Dentistry, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra, India
| | - Avinash Kharat
- Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra, India
| | - Ramesh Bhonde
- Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra, India
| | - Vinita C. Patole
- Department of Pharmaceutics, Dr. D.Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra, India
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Kong Q, Wang Y, Jiang N, Wang Y, Wang R, Hu X, Mao J, Shi X. Exosomes as Promising Therapeutic Tools for Regenerative Endodontic Therapy. Biomolecules 2024; 14:330. [PMID: 38540750 PMCID: PMC10967740 DOI: 10.3390/biom14030330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 03/03/2024] [Accepted: 03/08/2024] [Indexed: 11/06/2024] Open
Abstract
Pulpitis is a common and frequent disease in dental clinics. Although vital pulp therapy and root canal treatment can stop the progression of inflammation, they do not allow for genuine structural regeneration and functional reconstruction of the pulp-dentin complex. In recent years, with the development of tissue engineering and regenerative medicine, research on stem cell-based regenerative endodontic therapy (RET) has achieved satisfactory preliminary results, significantly enhancing its clinical translational prospects. As one of the crucial paracrine effectors, the roles and functions of exosomes in pulp-dentin complex regeneration have gained considerable attention. Due to their advantages of cost-effectiveness, extensive sources, favorable biocompatibility, and high safety, exosomes are considered promising therapeutic tools to promote dental pulp regeneration. Accordingly, in this article, we first focus on the biological properties of exosomes, including their biogenesis, uptake, isolation, and characterization. Then, from the perspectives of cell proliferation, migration, odontogenesis, angiogenesis, and neurogenesis, we aim to reveal the roles and mechanisms of exosomes involved in regenerative endodontics. Lastly, immense efforts are made to illustrate the clinical strategies and influencing factors of exosomes applied in dental pulp regeneration, such as types of parental cells, culture conditions of parent cells, exosome concentrations, and scaffold materials, in an attempt to lay a solid foundation for exploring and facilitating the therapeutic strategy of exosome-based regenerative endodontic procedures.
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Affiliation(s)
- Qingyue Kong
- Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Q.K.); (Y.W.); (Y.W.); (R.W.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Yujie Wang
- Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Q.K.); (Y.W.); (Y.W.); (R.W.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Nan Jiang
- Central Laboratory, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing 100081, China;
| | - Yifan Wang
- Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Q.K.); (Y.W.); (Y.W.); (R.W.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Rui Wang
- Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Q.K.); (Y.W.); (Y.W.); (R.W.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Xiaohan Hu
- Outpatient Department Office, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;
| | - Jing Mao
- Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Q.K.); (Y.W.); (Y.W.); (R.W.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Xin Shi
- Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Q.K.); (Y.W.); (Y.W.); (R.W.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
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Zhang S, Wang S, Chen J, Cui Y, Lu X, Xiong S, Yue C, Yang B. Human dental pulp stem cell-derived exosomes decorated titanium scaffolds for promoting bone regeneration. Colloids Surf B Biointerfaces 2024; 235:113775. [PMID: 38330688 DOI: 10.1016/j.colsurfb.2024.113775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 01/21/2024] [Accepted: 01/31/2024] [Indexed: 02/10/2024]
Abstract
Exosomes, nanoscale extracellular vesicles crucial for intercellular communication, hold great promise as a therapeutic avenue in cell-free tissue regeneration. In this study, we identified and utilized exosomes to adorn anodized titanium scaffolds, inducing osteogenic differentiation in human dental pulp stem cells (hDPSCs). The osteogenesis of hDPSCs was stimulated by exosomes derived from hDPSCs that underwent various periods of osteogenic differentiation. After purification, these exosomes were loaded onto anodized titanium scaffolds. Notably, the scaffolds loaded with exosomes deriving from osteogenic differentiated hDPSCs demonstrated superior bone tissue regeneration compared to those loaded with exosomes deriving from hDPSCs within 10-week. RNA-sequencing analysis shed light on the underlying mechanism, revealing that the osteogenic exosomes carried specific cargo, which is due to upregulated miRNAs (Hsa-miR-29c-5p, Hsa-miR-378a-5p, Hsa-miR-10b-5p and Hsa-miR-9-3p) associated with osteogenesis. And down-regulated anti-osteogenic miRNA (Hsa-miR-31-3p, Hsa-miR-221-3p, Hsa-miR-183-5p and Hsa-miR-503-5p). In conclusion, the identification and utilization of exosomes derived from osteogenic differentiated stem cells offer a novel and promising strategy for achieving cell-free bone regeneration.
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Affiliation(s)
- Siqi Zhang
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China; National Engineering Research Center for Biomaterials, Chengdu 610064, People's Republic of China; College of Biomedical Engineering, Sichuan University, Chengdu 610064, People's Republic of China
| | - Simeng Wang
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China; National Engineering Research Center for Biomaterials, Chengdu 610064, People's Republic of China; College of Biomedical Engineering, Sichuan University, Chengdu 610064, People's Republic of China
| | - Jun Chen
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China; National Engineering Research Center for Biomaterials, Chengdu 610064, People's Republic of China; College of Biomedical Engineering, Sichuan University, Chengdu 610064, People's Republic of China
| | - Yifan Cui
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China; National Engineering Research Center for Biomaterials, Chengdu 610064, People's Republic of China; College of Biomedical Engineering, Sichuan University, Chengdu 610064, People's Republic of China
| | - Xugang Lu
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China; National Engineering Research Center for Biomaterials, Chengdu 610064, People's Republic of China; College of Biomedical Engineering, Sichuan University, Chengdu 610064, People's Republic of China
| | - Shibing Xiong
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China; National Engineering Research Center for Biomaterials, Chengdu 610064, People's Republic of China; College of Biomedical Engineering, Sichuan University, Chengdu 610064, People's Republic of China
| | - Chongxia Yue
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China; National Engineering Research Center for Biomaterials, Chengdu 610064, People's Republic of China; NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterial & Institute of Regulatory Science for Medical Devices & NMPA Research Base of Regulatory Science for Medical Devices, Sichuan University, Chengdu 610064, People's Republic of China; College of Biomedical Engineering, Sichuan University, Chengdu 610064, People's Republic of China.
| | - Bangcheng Yang
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China; National Engineering Research Center for Biomaterials, Chengdu 610064, People's Republic of China; College of Biomedical Engineering, Sichuan University, Chengdu 610064, People's Republic of China.
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Santilli F, Fabrizi J, Santacroce C, Caissutti D, Spinello Z, Candelise N, Lancia L, Pulcini F, Delle Monache S, Mattei V. Analogies and Differences Between Dental Stem Cells: Focus on Secretome in Combination with Scaffolds in Neurological Disorders. Stem Cell Rev Rep 2024; 20:159-174. [PMID: 37962698 PMCID: PMC10799818 DOI: 10.1007/s12015-023-10652-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/02/2023] [Indexed: 11/15/2023]
Abstract
Mesenchymal stem cells (MSCs) are well known for their beneficial effects, differentiation capacity and regenerative potential. Dental-derived MSCs (DSCs) are more easily accessible and have a non-invasive isolation method rather than MSCs isolated from other sources (umbilical cord, bone marrow, and adipose tissue). In addition, DSCs appear to have a relevant neuro-regenerative potential due to their neural crest origin. However, it is now known that the beneficial effects of MSCs depend, at least in part, on their secretome, referring to all the bioactive molecules (neurotrophic factors) released in the conditioned medium (CM) or in the extracellular vesicles (EVs) in particular exosomes (Exos). In this review, we described the similarities and differences between various DSCs. Our focus was on the secretome of DSCs and their applications in cell therapy for neurological disorders. For neuro-regenerative purposes, the secretome of different DSCs has been tested. Among these, the secretome of dental pulp stem cells and stem cells from human exfoliated deciduous teeth have been the most widely studied. Both CM and Exos obtained from DSCs have been shown to promote neurite outgrowth and neuroprotective effects as well as their combination with scaffold materials (to improve their functional integration in the tissue). For these reasons, the secretome obtained from DSCs in combination with scaffold materials may represent a promising tissue engineering approach for neuroprotective and neuro-regenerative treatments.
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Affiliation(s)
- Francesca Santilli
- Biomedicine and Advanced Technologies Rieti Center, "Sabina Universitas", Via A.M. Ricci 35/A, 02100, Rieti, Italy
| | - Jessica Fabrizi
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Costantino Santacroce
- Biomedicine and Advanced Technologies Rieti Center, "Sabina Universitas", Via A.M. Ricci 35/A, 02100, Rieti, Italy
| | - Daniela Caissutti
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Zaira Spinello
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Niccolò Candelise
- National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 29900161, Rome, Italy
| | - Loreto Lancia
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy
| | - Fanny Pulcini
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy
| | - Simona Delle Monache
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy.
| | - Vincenzo Mattei
- Dipartimento di Scienze della Vita, della Salute e delle Professioni Sanitarie, Link Campus University, Via del Casale di San Pio V 44, 00165, Rome, Italy.
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Mohd Nor NH, Mansor NI, Mohd Kashim MIA, Mokhtar MH, Mohd Hatta FA. From Teeth to Therapy: A Review of Therapeutic Potential within the Secretome of Stem Cells from Human Exfoliated Deciduous Teeth. Int J Mol Sci 2023; 24:11763. [PMID: 37511524 PMCID: PMC10380442 DOI: 10.3390/ijms241411763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/18/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023] Open
Abstract
Stem cells derived from human exfoliated deciduous teeth (SHED) have emerged as an alternative stem cell source for cell therapy and regenerative medicine because they are readily available, pose fewer ethical concerns, and have low immunogenicity and tumourigenicity. SHED offer a number of advantages over other dental stem cells, including a high proliferation rate with the potential to differentiate into multiple developmental lineages. The therapeutic effects of SHED are mediated by multiple mechanisms, including immunomodulation, angiogenesis, neurogenesis, osteogenesis, and adipogenesis. In recent years, there is ample evidence that the mechanism of action of SHED is mainly due to its paracrine action, releasing a wide range of soluble factors such as cytokines, chemokines, and trophic factors (also known as 'secretome') into the local tissue microenvironment to promote tissue survival and recovery. This review provides an overview of the secretome derived from SHED and highlights the bioactive molecules involved in tissue regeneration and their potential applications in regenerative medicine.
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Affiliation(s)
- Nurul Hafizah Mohd Nor
- Institute of Islamic Civilization, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor Darul Ehsan, Malaysia
| | - Nur Izzati Mansor
- Department of Nursing, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Kuala Lumpur, Malaysia
| | - Mohd Izhar Ariff Mohd Kashim
- Institute of Islamic Civilization, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor Darul Ehsan, Malaysia
- Faculty of Islamic Studies, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor Darul Ehsan, Malaysia
| | - Mohd Helmy Mokhtar
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Kuala Lumpur, Malaysia
| | - Farah Ayuni Mohd Hatta
- Institute of Islamic Civilization, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor Darul Ehsan, Malaysia
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Dżaman K, Czerwaty K. Extracellular Vesicle-Based Drug Delivery Systems for Head and Neck Squamous Cell Carcinoma: A Systematic Review. Pharmaceutics 2023; 15:pharmaceutics15051327. [PMID: 37242569 DOI: 10.3390/pharmaceutics15051327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 04/07/2023] [Accepted: 04/21/2023] [Indexed: 05/28/2023] Open
Abstract
It is estimated that there are over 890,000 new cases of head and neck squamous cell carcinoma (HNSCC) worldwide each year, accounting for approximately 5% of all cancer cases. Current treatment options for HNSCC often cause significant side effects and functional impairments, thus there is a challenge to discover more acceptable treatment technologies. Extracellular vesicles (EVs) can be utilized for HNSCC treatment in several ways, for example, for drug delivery, immune modulation, as biomarkers for diagnostics, gene therapy, or tumor microenvironment modulation. This systematic review summarizes new knowledge regarding these options. Articles published up to 11 December 2022, were identified by searching the electronic databases PubMed/MEDLINE, Scopus, Web of Science, and Cochrane. Only full-text original research papers written in English were considered eligible for analysis. The quality of studies was assessed using the Office of Health Assessment and Translation (OHAT) Risk of Bias Rating Tool for Human and Animal Studies, modified for the needs of this review. Of 436 identified records, 18 were eligible and included. It is important to note that the use of EVs as a treatment for HNSCC is still in the early stages of research, so we summarized information on challenges such as EV isolation, purification, and standardization of EV-based therapies in HNSCC.
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Affiliation(s)
- Karolina Dżaman
- Department of Otolaryngology, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, Poland
| | - Katarzyna Czerwaty
- Department of Otolaryngology, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, Poland
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10
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Zeng Y, Liu L, Huang D, Song D. Immortalized cell lines derived from dental/odontogenic tissue. Cell Tissue Res 2023:10.1007/s00441-023-03767-5. [PMID: 37039940 DOI: 10.1007/s00441-023-03767-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 03/16/2023] [Indexed: 04/12/2023]
Abstract
Stem cells derived from dental/odontogenic tissue have the property of multiple differentiation and are prospective in tooth regenerative medicine and cellular and molecular studies. However, in the face of cellular senescence soon in vitro, the proliferation ability of the cells is limited, so studies are hindered to some extent. Fortunately, immortalization strategies are expected to solve the above issues. Cellular immortalization is that cells are immortalized by introducing oncogenes, human telomerase reverse transcriptase genes (hTERT), or miscellaneous immortalization genes to get unlimited proliferation. At present, a variety of immortalized stem cells from dental/odontogenic tissue has been successfully generated, such as dental pulp stem cells (DPSCs), periodontal ligament cells (PDLs), stem cells from human exfoliated deciduous teeth (SHEDs), dental papilla cells (DPCs), and tooth germ mesenchymal cells (TGMCs). This review summarized establishment and applications of immortalized stem cells from dental/odontogenic tissues and then discussed the advantages and challenges of immortalization.
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Affiliation(s)
- Yanglin Zeng
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Center for Stomatology, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Liu Liu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Center for Stomatology, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Dingming Huang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Center for Stomatology, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
- Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Dongzhe Song
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Center for Stomatology, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
- Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
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11
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Guo J, Yao H, Li X, Chang L, Wang Z, Zhu W, Su Y, Qin L, Xu J. Advanced Hydrogel systems for mandibular reconstruction. Bioact Mater 2023; 21:175-193. [PMID: 36093328 PMCID: PMC9413641 DOI: 10.1016/j.bioactmat.2022.08.001] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 07/16/2022] [Accepted: 08/02/2022] [Indexed: 12/23/2022] Open
Abstract
Mandibular defect becomes a prevalent maxillofacial disease resulting in mandibular dysfunctions and huge psychological burdens to the patients. Considering the routine presence of oral contaminations and aesthetic restoration of facial structures, the current clinical treatments are however limited, incapable to reconstruct the structural integrity and regeneration, spurring the need for cost-effective mandibular tissue engineering. Hydrogel systems possess great merit for mandibular reconstruction with precise involvement of cells and bioactive factors. In this review, current clinical treatments and distinct mode(s) of mandible formation and pathological resorption are summarized, followed by a review of hydrogel-related mandibular tissue engineering, and an update on the advanced fabrication of hydrogels with improved mechanical property, antibacterial ability, injectable form, and 3D bioprinted hydrogel constructs. The exploration of advanced hydrogel systems will lay down a solid foundation for a bright future with more biocompatible, effective, and personalized treatment in mandibular reconstruction.
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Affiliation(s)
- Jiaxin Guo
- Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
- Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Hao Yao
- Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
- Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Xu Li
- Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
- Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Liang Chang
- Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
- Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Zixuan Wang
- Department of Mechanical Engineering, Tsinghua University, Beijing, China
| | - Wangyong Zhu
- Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China
| | - Yuxiong Su
- Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China
| | - Ling Qin
- Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
- Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
- Corresponding author. Director of Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.
| | - Jiankun Xu
- Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
- Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
- Corresponding author. Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.
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12
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Liu F, Sun T, An Y, Ming L, Li Y, Zhou Z, Shang F. The potential therapeutic role of extracellular vesicles in critical-size bone defects: Spring of cell-free regenerative medicine is coming. Front Bioeng Biotechnol 2023; 11:1050916. [PMID: 36733961 PMCID: PMC9887316 DOI: 10.3389/fbioe.2023.1050916] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 01/02/2023] [Indexed: 01/19/2023] Open
Abstract
In recent years, the incidence of critical-size bone defects has significantly increased. Critical-size bone defects seriously affect patients' motor functions and quality of life and increase the need for additional clinical treatments. Bone tissue engineering (BTE) has made great progress in repairing critical-size bone defects. As one of the main components of bone tissue engineering, stem cell-based therapy is considered a potential effective strategy to regenerate bone tissues. However, there are some disadvantages including phenotypic changes, immune rejection, potential tumorigenicity, low homing efficiency and cell survival rate that restrict its wider clinical applications. Evidence has shown that the positive biological effects of stem cells on tissue repair are largely mediated through paracrine action by nanostructured extracellular vesicles (EVs), which may overcome the limitations of traditional stem cell-based treatments. In addition to stem cell-derived extracellular vesicles, the potential therapeutic roles of nonstem cell-derived extracellular vesicles in critical-size bone defect repair have also attracted attention from scholars in recent years. Currently, the development of extracellular vesicles-mediated cell-free regenerative medicine is still in the preliminary stage, and the specific mechanisms remain elusive. Herein, the authors first review the research progress and possible mechanisms of extracellular vesicles combined with bone tissue engineering scaffolds to promote bone regeneration via bioactive molecules. Engineering modified extracellular vesicles is an emerging component of bone tissue engineering and its main progression and clinical applications will be discussed. Finally, future perspectives and challenges of developing extracellular vesicle-based regenerative medicine will be given. This review may provide a theoretical basis for the future development of extracellular vesicle-based biomedicine and provide clinical references for promoting the repair of critical-size bone defects.
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Affiliation(s)
- Fen Liu
- Department of Periodontology, Shenzhen Stomatological Hospital (Pingshan), Southern Medical University, Shenzhen, Guangdong, China
| | - Tianyu Sun
- Department of Periodontology, Stomatological Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Ying An
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture and Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi’an, Shaanxi, China
| | - Leiguo Ming
- Department of Research and Development, Shaanxi Zhonghong Institute of Regenerative Medicine, Xi’an, Shaanxi, China
| | - Yinghui Li
- Department of Orthodontics, Stomatological Hospital, Hebei Medical University, Shijiazhuang, Hebei, China
| | - Zhifei Zhou
- Department of Stomatology, General Hospital of Tibetan Military Command, Lhasa, Tibet, China,*Correspondence: Fengqing Shang, ; Zhifei Zhou,
| | - Fengqing Shang
- Department of Stomatology, Air Force Medical Center, Fourth Military Medical University, Beijing, China,*Correspondence: Fengqing Shang, ; Zhifei Zhou,
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13
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Neural Regeneration in Regenerative Endodontic Treatment: An Overview and Current Trends. Int J Mol Sci 2022; 23:ijms232415492. [PMID: 36555133 PMCID: PMC9779866 DOI: 10.3390/ijms232415492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 11/24/2022] [Accepted: 12/01/2022] [Indexed: 12/12/2022] Open
Abstract
Pulpal and periapical diseases are the most common dental diseases. The traditional treatment is root canal therapy, which achieves satisfactory therapeutic outcomes-especially for mature permanent teeth. Apexification, pulpotomy, and pulp revascularization are common techniques used for immature permanent teeth to accelerate the development of the root. However, there are obstacles to achieving functional pulp regeneration. Recently, two methods have been proposed based on tissue engineering: stem cell transplantation, and cell homing. One of the goals of functional pulp regeneration is to achieve innervation. Nerves play a vital role in dentin formation, nutrition, sensation, and defense in the pulp. Successful neural regeneration faces tough challenges in both animal studies and clinical trials. Investigation of the regeneration and repair of the nerves in the pulp has become a serious undertaking. In this review, we summarize the current understanding of the key stem cells, signaling molecules, and biomaterials that could promote neural regeneration as part of pulp regeneration. We also discuss the challenges in preclinical or clinical neural regeneration applications to guide deep research in the future.
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14
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Sivolella S, Scanu A, Xie Z, Vianello S, Stellini E. Biobanking in dentistry: A review. JAPANESE DENTAL SCIENCE REVIEW 2022; 58:31-40. [PMID: 35024075 PMCID: PMC8728430 DOI: 10.1016/j.jdsr.2021.12.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 12/14/2021] [Accepted: 12/20/2021] [Indexed: 01/13/2023] Open
Abstract
Biobanks are not-for-profit services for the collection, processing, storage and distribution of biological samples and data for research and diagnostic purposes. In dentistry, biological materials and data obtained from questionnaires investigating oral conditions can be stored and used for large-scale studies on oral and systemic diseases. To give some examples: gene expression microarrays obtained on biobanked specimens were used in the identification of genetic alterations in oral cancer; efforts to identify genetic mechanisms behind dental caries have been based on an integrative analysis of transcriptome-wide associations and messenger RNA expression. One of the largest studies on facial pain was conducted using Biobank data. Cryopreservation of dental pulp stem cells is a common practice in tooth biobanks. With the exception of teeth and pulp, also leftover oral soft and hard tissues may represent a source of healthy samples that has rarely been exploited as yet. While biobanks are increasingly attracting the attention of the scientific community and becoming economically sustainable, a systematic approach to this resource in dentistry seems to be lacking. This review illustrates the applications of biobanking in dentistry, describing biobanked pathological and healthy samples and data, and discussing future developments.
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Affiliation(s)
- Stefano Sivolella
- Department of Neuroscience, Dentistry Section, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
| | - Anna Scanu
- Department of Neuroscience, Dentistry Section, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
| | - Zijing Xie
- Department of Neuroscience, Dentistry Section, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
| | - Sara Vianello
- Department of Neuroscience, Neuromuscular Center, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
| | - Edoardo Stellini
- Department of Neuroscience, Dentistry Section, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
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15
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Guo Z, Zhang Y, Yan F. Potential of Mesenchymal Stem Cell-Based Therapies for Pulmonary Fibrosis. DNA Cell Biol 2022; 41:951-965. [DOI: 10.1089/dna.2022.0327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Zhihou Guo
- Stem Cell Lab, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Yaping Zhang
- Center for Molecular Diagnosis and Therapy, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Furong Yan
- Center for Molecular Diagnosis and Therapy, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
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16
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Ziauddin SM, Nakashima M, Watanabe H, Tominaga M, Iohara K. Biological characteristics and pulp regeneration potential of stem cells from canine deciduous teeth compared with those of permanent teeth. Stem Cell Res Ther 2022; 13:439. [PMID: 36056397 PMCID: PMC9438285 DOI: 10.1186/s13287-022-03124-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 08/05/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Clinical studies have demonstrated that dental pulp stem cells isolated from permanent teeth (PT-DPSCs) are safe and efficacious for complete pulp regeneration in mature pulpectomized permanent teeth with complete apical closure. Moreover, dental pulp stem cells from deciduous teeth (DT-DPSCs) have also been shown to be useful for pulp regenerative cell therapy of injured immature permanent teeth. However, direct comparisons of the pulp regenerative potential of DT-DPSCs and PT-DPSCs from the same individual have not been performed. This study aimed to compare the differences in stem cell properties and pulp regenerative potential of DT-DPSCs and PT-DPSCs of identical origin. METHODS DT-DPSCs and PT-DPSCs were isolated from the same individual dogs at 4 months and 9 months of age, respectively. The expression of cell surface antigen markers, proliferation and migration activities, and gene expression of stem cell markers, angiogenic/neurotrophic factors and senescence markers were compared. The effects of conditioned medium (CM) derived from these cells on cellular proliferation, migration, angiogenesis, neurite outgrowth and immunosuppression were also compared. Autologous transplantation of DT-DPSCs or PT-DPSCs together with G-CSF was performed to treat pulpectomized teeth in individual dogs. The vascularization and reinnervation of the regenerated pulp tissues were qualitatively and quantitatively compared between groups by histomorphometric analyses. RESULTS The rates of positive CXCR4 and G-CSFR expression in DT-DPSCs were significantly higher than those in PT-DPSCs. DT-DPSCs migrated at a higher rate with/without G-CSF and exhibited increased expression of the stem cell markers Oct3/4 and CXCR4 and the angiogenic factor VEGF and decreased expression of the senescence marker p16 than PT-DPSCs. DT-DPSC-derived CM promoted increased cell proliferation, migration with G-CSF, and angiogenesis compared with PT-DPSC-derived CM; however, no difference was observed in neurite outgrowth or immunosuppression. The regenerated pulp tissues in the pulpectomized teeth were quantitatively and qualitatively similar between the DT-DPSCs and PT-DPSCs transplant groups. CONCLUSIONS These results demonstrated that DT-DPSCs could be a potential clinical alternative to PT-DPSCs for pulp regenerative therapy. DT-DPSCs can be preserved in an individual cell bank and used for potential future pulp regenerative therapy before the supply of an individual's own sound discarded teeth has been exhausted.
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Affiliation(s)
- S M Ziauddin
- Regenerative Dental Medicine, National Center for Geriatrics and Gerontology, Research Institute, Geroscience Research Center, 7-430 Morioka, Obu, Aichi, 474-8511, Japan
- Department of Periodontology and Endodontology, Nagasaki University Graduate, School of Biomedical Sciences, Nagasaki, Japan
| | - Misako Nakashima
- Regenerative Dental Medicine, National Center for Geriatrics and Gerontology, Research Institute, Geroscience Research Center, 7-430 Morioka, Obu, Aichi, 474-8511, Japan
- Aeras Bio Inc., Air Water Group, Kobe, Hyogo, 650-047, Japan
| | - Hideto Watanabe
- Institute for Molecular Science of Medicine, Aichi Medical University, Nagakute, Aichi, 480-1195, Japan
| | - Michiyo Tominaga
- Regenerative Dental Medicine, National Center for Geriatrics and Gerontology, Research Institute, Geroscience Research Center, 7-430 Morioka, Obu, Aichi, 474-8511, Japan
| | - Koichiro Iohara
- Regenerative Dental Medicine, National Center for Geriatrics and Gerontology, Research Institute, Geroscience Research Center, 7-430 Morioka, Obu, Aichi, 474-8511, Japan.
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Wang D, Cao H, Hua W, Gao L, Yuan Y, Zhou X, Zeng Z. Mesenchymal Stem Cell-Derived Extracellular Vesicles for Bone Defect Repair. MEMBRANES 2022; 12:membranes12070716. [PMID: 35877919 PMCID: PMC9315966 DOI: 10.3390/membranes12070716] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/17/2022] [Accepted: 07/18/2022] [Indexed: 12/12/2022]
Abstract
The repair of critical bone defects is a hotspot of orthopedic research. With the development of bone tissue engineering (BTE), there is increasing evidence showing that the combined application of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) (MSC-EVs), especially exosomes, with hydrogels, scaffolds, and other bioactive materials has made great progress, exhibiting a good potential for bone regeneration. Recent studies have found that miRNAs, proteins, and other cargo loaded in EVs are key factors in promoting osteogenesis and angiogenesis. In BTE, the expression profile of the intrinsic cargo of EVs can be changed by modifying the gene expression of MSCs to obtain EVs with enhanced osteogenic activity and ultimately enhance the osteoinductive ability of bone graft materials. However, the current research on MSC-EVs for repairing bone defects is still in its infancy, and the underlying mechanism remains unclear. Therefore, in this review, the effect of bioactive materials such as hydrogels and scaffolds combined with MSC-EVs in repairing bone defects is summarized, and the mechanism of MSC-EVs promoting bone defect repair by delivering active molecules such as internal miRNAs is further elucidated, which provides a theoretical basis and reference for the clinical application of MSC-EVs in repairing bone defects.
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Affiliation(s)
- Dongxue Wang
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China; (D.W.); (W.H.); (L.G.)
| | - Hong Cao
- School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China; (H.C.); (Y.Y.)
| | - Weizhong Hua
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China; (D.W.); (W.H.); (L.G.)
| | - Lu Gao
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China; (D.W.); (W.H.); (L.G.)
| | - Yu Yuan
- School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China; (H.C.); (Y.Y.)
| | - Xuchang Zhou
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China; (D.W.); (W.H.); (L.G.)
- School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China; (H.C.); (Y.Y.)
- Correspondence: (X.Z.); (Z.Z.)
| | - Zhipeng Zeng
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China; (D.W.); (W.H.); (L.G.)
- Correspondence: (X.Z.); (Z.Z.)
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18
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Aly RM, Aglan HA, Eldeen GN, Mahmoud NS, Aboul-Ezz EH, Ahmed HH. Efficient generation of functional pancreatic β cells from dental-derived stem cells via laminin-induced differentiation. J Genet Eng Biotechnol 2022; 20:85. [PMID: 35674918 PMCID: PMC9177930 DOI: 10.1186/s43141-022-00369-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 05/20/2022] [Indexed: 11/15/2022]
Abstract
BACKGROUND This study was designed to generate functional insulin-producing cells (IPCs) from dental-derived mesenchymal stem cells (MSCs) and further explore their therapeutic potential against diabetes mellitus in vivo. MSCs were isolated from human dental pulp and periodontal ligament and were induced to differentiate into insulin-producing cells (IPCs) using laminin-based differentiation protocol for 14 days. Confirmation of IPCs was performed through real-time PCR analysis and insulin release assay. Then, the generated IPCs were labeled with PKH26 dye prior to transplantation in experimental animals. Twenty-eight days later, blood glucose, serum insulin (INS), c-peptide (CP), and visfatin (VF) levels and pancreatic glucagon (GC) level were estimated. Pancreatic forkhead box protein A2 (Foxa2) and SRY-box transcription factor 17 (Sox17), insulin-like growth factor I (IGF-1), and fibroblast growth factor10 (FGF 10) gene expression levels were analyzed. RESULTS Dental stem cells were successfully differentiated into IPCs that demonstrated increased expression of pancreatic endocrine genes. IPCs released insulin after being subjected to high levels of glucose. In vivo findings uncovered that the implanted IPCs triggered significant decrease in blood glucose, serum VF, and pancreatic GC levels with significant increase in serum INS and CP levels. Furthermore, the implanted IPCs provoked significant upregulation in the expression level of pancreatic genes. Histopathological description of the pancreas tissues revealed that transplantation of IPCs ameliorated the destabilization of pancreas tissue architecture. CONCLUSION This study demonstrates the significant role of the implantation of IPCs generated from dental-derived stem cells in treatment of diabetes mellitus.
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Affiliation(s)
- Riham M Aly
- Basic Dental Science Department, Oral Medicine & Dentistry Research Institute, National Research Centre, Dokki, Giza, Egypt.
- Stem Cell Laboratory, Center of Excellence for Advanced Sciences, National Research Centre, 33 El Buhouth St., Dokki, 12622, Giza, Egypt.
| | - Hadeer A Aglan
- Stem Cell Laboratory, Center of Excellence for Advanced Sciences, National Research Centre, 33 El Buhouth St., Dokki, 12622, Giza, Egypt
- Hormones Department, Medicine Research and Clinical Studies Institute, National Research Centre, Dokki, Giza, Egypt
| | - Ghada Nour Eldeen
- Molecular Genetics & Enzymology Department, Human Genetic & Genome Research Institute, National Research Centre, Dokki, Giza, Egypt
| | - Nadia S Mahmoud
- Stem Cell Laboratory, Center of Excellence for Advanced Sciences, National Research Centre, 33 El Buhouth St., Dokki, 12622, Giza, Egypt
- Hormones Department, Medicine Research and Clinical Studies Institute, National Research Centre, Dokki, Giza, Egypt
| | - Eman H Aboul-Ezz
- Basic Dental Science Department, Oral Medicine & Dentistry Research Institute, National Research Centre, Dokki, Giza, Egypt
- Stem Cell Laboratory, Center of Excellence for Advanced Sciences, National Research Centre, 33 El Buhouth St., Dokki, 12622, Giza, Egypt
| | - Hanaa H Ahmed
- Stem Cell Laboratory, Center of Excellence for Advanced Sciences, National Research Centre, 33 El Buhouth St., Dokki, 12622, Giza, Egypt
- Hormones Department, Medicine Research and Clinical Studies Institute, National Research Centre, Dokki, Giza, Egypt
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19
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Cho YD, Kim KH, Lee YM, Ku Y, Seol YJ. Dental-derived cells for regenerative medicine: stem cells, cell reprogramming, and transdifferentiation. J Periodontal Implant Sci 2022; 52:437-454. [PMID: 36468465 PMCID: PMC9807848 DOI: 10.5051/jpis.2103760188] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 12/08/2021] [Accepted: 01/24/2022] [Indexed: 01/07/2023] Open
Abstract
Embryonic stem cells have been a popular research topic in regenerative medicine owing to their pluripotency and applicability. However, due to the difficulty in harvesting them and their low yield efficiency, advanced cell reprogramming technology has been introduced as an alternative. Dental stem cells have entered the spotlight due to their regenerative potential and their ability to be obtained from biological waste generated after dental treatment. Cell reprogramming, a process of reverting mature somatic cells into stem cells, and transdifferentiation, a direct conversion between different cell types without induction of a pluripotent state, have helped overcome the shortcomings of stem cells and raised interest in their regenerative potential. Furthermore, the potential of these cells to return to their original cell types due to their epigenetic memory has reinforced the need to control the epigenetic background for successful management of cellular differentiation. Herein, we discuss all available sources of dental stem cells, the procedures used to obtain these cells, and their ability to differentiate into the desired cells. We also introduce the concepts of cell reprogramming and transdifferentiation in terms of genetics and epigenetics, including DNA methylation, histone modification, and non-coding RNA. Finally, we discuss a novel therapeutic avenue for using dental-derived cells as stem cells, and explain cell reprogramming and transdifferentiation, which are used in regenerative medicine and tissue engineering.
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Affiliation(s)
- Young-Dan Cho
- Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital, Seoul, Korea
| | - Kyoung-Hwa Kim
- Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital, Seoul, Korea
| | - Yong-Moo Lee
- Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital, Seoul, Korea
| | - Young Ku
- Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital, Seoul, Korea
| | - Yang-Jo Seol
- Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital, Seoul, Korea
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Yong Z, Kuang G, Fengying S, Shoumei X, Duohong Z, Jiacai H, Xuyan T. Comparison of the Angiogenic Ability between SHED and DPSC in a Mice Model with Critical Limb Ischemic. Tissue Eng Regen Med 2022; 19:861-870. [PMID: 35474506 PMCID: PMC9294125 DOI: 10.1007/s13770-022-00452-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 02/14/2022] [Accepted: 03/09/2022] [Indexed: 10/18/2022] Open
Abstract
BACKGROUND Regenerative medicine by using stem cells from dental pulp is promising for treating patients with critical limb ischemic (CLI). Here, we investigated the difference in the angiogenetic ability of stem cells from human exfoliated deciduous teeth (SHED) and human dental pulp stem cells (DPSC). METHODS SHED and DPSC were harvested from dental pulp and analyzed in flow- cytometry for detecting the expression of surface markers. Levels of angiogenetic marker were examined by RT-PCR and Western-blot. Eighteen immunodeficient mice of critical limb ischemic model were divided into three groups: SHED, DPSC and saline, which was administered with SHED, DPSC or saline intramuscularly. Histological examination was performed to detect the regenerative results. RESULTS A highly expression of CD146 was detected in SHED. Moreover, cells with negative expression of both CD146 and CD31 in SHED were more in comparison with those in DPSC. Expression of angiogenesis factors including CXCL12, CXCR4, Hif-1a, CD31, VEGF and bFGF were significant higher in SHED than DPSC by the RT-PCR and Western-Blot results. SHED induced more CD31 expression and less fibrous tissue formation in the critical limb ischemic model as compare with DPSC and saline. CONCLUSION Both SHED and DPSC possessed the ability of repairing CLI. With expressing more proangiogenesis factors, SHED may have the advantage of repairing CLI.
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Affiliation(s)
- Zhou Yong
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China.,Department of Dental Implantology, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China.,Periodontal Department College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Gu Kuang
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China.,Periodontal Department College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Sun Fengying
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China.,Periodontal Department College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Xuan Shoumei
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China.,Periodontal Department College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Zou Duohong
- Department of Oral Surgery, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of Stomatology, School of Medicine, Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200011, China.,Periodontal Department College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - He Jiacai
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China.,Department of Dental Implantology, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China.,Periodontal Department College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Tang Xuyan
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China.
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21
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Su J, Ge X, Jiang N, Zhang Z, Wu X. Efficacy of Mesenchymal Stem Cells from Human Exfoliated DeciduousTeeth and their Derivatives in Inflammatory Diseases Therapy. Curr Stem Cell Res Ther 2022; 17:302-316. [PMID: 35440314 DOI: 10.2174/1574888x17666220417153309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 02/01/2022] [Accepted: 02/28/2022] [Indexed: 11/22/2022]
Abstract
Mesenchymal stem cells derived from postnatal orofacial tissues can be readily isolated and possess diverse origins, for example, from surgically removed teeth or gingiva. These cells exhibit stem cell properties, strong potential for self-renewal, and show multi-lineage differentiation, and they have therefore been widely employed in stem cell therapy, tissue regeneration, and inflammatory diseases. Among them, stem cells from human exfoliated deciduous teeth [SHED] and their derivatives have manifested wide application in the treatment of diseases because of their outstanding advantages- including convenient access, easy storage, and less immune rejection. Numerous studies have shown that most diseases are closely associated with inflammation and that inflammatory diseases are extremely destructive, can lead to necrosis of organ parenchymal cells, and can deposit excessive extracellular ma- trix in the tissues. Inflammatory diseases are thus the principal causes of disability and death from many diseases worldwide. SHED and their derivatives not only exhibit the basic characteristics of stem cells but also exhibit some special properties of their own, particularly with regard to their great potential in inhib- iting inflammation and tissue regeneration. SHED therapy may provide a new direction for the treatment of inflammation and corresponding tissue defects. In this review, we critically analyze and summarize the latest findings on the behaviors and functions of SHED, serum‑free conditioned medium from SHED [SHED-CM], and extracellular vesicles, especially exosomes, from SHED [SHED-Exos], and discuss their roles and underlying mechanisms in the control of inflammatory diseases, thus further highlighting additional functions for SHED and their derivatives in future therapies.
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Affiliation(s)
| | - Xuejun Ge
- Shanxi Medical University School and Hospital of Stomatology & Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan 030001, China
| | | | - Ziqian Zhang
- Shanxi Medical University School and Hospital of Stomatology & Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan 030001, China
| | - Xiaowen Wu
- Shanxi Medical University School and Hospital of Stomatology & Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan 030001, China
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22
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Liu P, Zhang Q, Mi J, Wang S, Xu Q, Zhuang D, Chen W, Liu C, Zhang L, Guo J, Wu X. Exosomes derived from stem cells of human deciduous exfoliated teeth inhibit angiogenesis in vivo and in vitro via the transfer of miR-100-5p and miR-1246. Stem Cell Res Ther 2022; 13:89. [PMID: 35241153 PMCID: PMC8895508 DOI: 10.1186/s13287-022-02764-9] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 12/29/2021] [Indexed: 12/14/2022] Open
Abstract
Background Anti-angiogenic therapy has been shown to be a promising strategy for anti-tumor treatment. Increasing evidence indicates that tumor angiogenesis is affected by exosomes that are secreted by mesenchymal stem cells (MSCs), but whether exosomes derived from MSCs suppress or promote angiogenesis remain paradoxical. The purpose of this study focused on understanding the potential role of exosomes derived from stem cells of human deciduous exfoliated teeth (SHED-Exos) in regulating angiogenesis and the underlying molecular mechanism. Methods Exosomes were isolated from supernatants of SHED cells using an exosome purification kit and were characterized by transmission electron microscopy, nanoparticle tracking analysis and western blot analysis. Cell Counting Kit-8, flow cytometric assays, western blots, wound healing and transwell migration assays were performed to characterize the roles of SHED-Exos on cell proliferation, apoptosis and migration of human umbilical vein endothelial cells (HUVECs). The anti-angiogenic activity of SHED-Exos was assessed via a tube formation assay of endothelial cells and angiogenesis-related factors were analyzed by western blotting. In vivo, we used the chick chorioallantoic membrane (CAM) assay and an oral squamous cell carcinoma (OSCC) xenograft transplantation model with nude mice that received multi-point injections at three-day intervals to evaluate the effects on angiogenesis. Furthermore, the sequencing of microRNAs (miRNAs) in SHED-Exos was performed to investigate the underlying anti-angiogenic mechanism. Results The results showed that SHED-Exos inhibit cell proliferation and migration and induce apoptosis in HUVECs. SHED-Exos suppress the tube-like structure formation of HUVECs in vitro. SHED-Exos downregulate several angiogenesis-related factors, including VEGFA, MMP-9 and ANGPT1. In vivo, the chick CAM assay verified that treatment with SHED-Exos inhibits micro-vascular formation, and importantly, significantly reduces the micro-vascular formation of tumors generated from xenografted OSCC cells, which was associated with the inhibition of tumor growth in vivo. Mechanistically, our data suggested that SHED-Exos are enriched with miR-100-5p and miR-1246 and are transferred to endothelial cells, which results in decreased tube formation via the down-regulation of VEGFA expression. Conclusions These results demonstrate that SHED-Exos inhibit angiogenesis in vitro and in vivo, which suggests that SHED-Exos could potentially serve as a novel and effective therapeutic approach for anti-angiogenic treatment. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-02764-9.
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Affiliation(s)
- Panpan Liu
- Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No.44-1 Wenhua Road West, Jinan, Shandong, China.,Department of Pediatrics Dentistry and Preventive Dentistry, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No.44-1 Wenhua Road West, Jinan, Shandong, China
| | - Qun Zhang
- Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No.44-1 Wenhua Road West, Jinan, Shandong, China
| | - Jun Mi
- Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No.44-1 Wenhua Road West, Jinan, Shandong, China
| | - Shuangshuang Wang
- Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No.44-1 Wenhua Road West, Jinan, Shandong, China
| | - Qiuping Xu
- Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No.44-1 Wenhua Road West, Jinan, Shandong, China.,Savaid Stomatology School of Hangzhou Medical College, Ningbo Stomatology Hospital, Ningbo, China
| | - Dexuan Zhuang
- Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No.44-1 Wenhua Road West, Jinan, Shandong, China
| | - Wenqian Chen
- Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No.44-1 Wenhua Road West, Jinan, Shandong, China.,Savaid Stomatology School of Hangzhou Medical College, Ningbo Stomatology Hospital, Ningbo, China
| | - Chang Liu
- Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No.44-1 Wenhua Road West, Jinan, Shandong, China.,Savaid Stomatology School of Hangzhou Medical College, Ningbo Stomatology Hospital, Ningbo, China
| | - Liwei Zhang
- Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No.44-1 Wenhua Road West, Jinan, Shandong, China.,Savaid Stomatology School of Hangzhou Medical College, Ningbo Stomatology Hospital, Ningbo, China
| | - Jing Guo
- Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No.44-1 Wenhua Road West, Jinan, Shandong, China. .,Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No.44-1 Wenhua Road West, Jinan, Shandong, China. .,Savaid Stomatology School of Hangzhou Medical College, Ningbo Stomatology Hospital, Ningbo, China.
| | - Xunwei Wu
- Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No.44-1 Wenhua Road West, Jinan, Shandong, China. .,Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. .,Savaid Stomatology School of Hangzhou Medical College, Ningbo Stomatology Hospital, Ningbo, China.
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23
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Glucose and Serum Deprivation Led to Altered Proliferation, Differentiation Potential and AMPK Activation in Stem Cells from Human Deciduous Tooth. J Pers Med 2021; 12:jpm12010018. [PMID: 35055333 PMCID: PMC8778212 DOI: 10.3390/jpm12010018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 12/19/2021] [Accepted: 12/21/2021] [Indexed: 11/16/2022] Open
Abstract
Stem cell therapy is an evolving treatment strategy in regenerative medicine. Recent studies report stem cells from human exfoliated deciduous teeth could complement the traditional mesenchymal stem cell sources. Stem cells from human exfoliated deciduous teeth exhibit mesenchymal characteristics with multilineage differentiation potential. Mesenchymal stem cells are widely investigated for cell therapy and disease modeling. Although many research are being conducted to address the challenges of mesenchymal stem cell therapy in clinics, most of the studies are still in infancy. Host cell microenvironment is one of the major factors affecting the homing of transplanted stem cell and understanding the factors affecting the fate of stem cells of prime important. In this study we aimed to understand the effects of serum deprivation in stem cells derived from human deciduous tooth. Our study aimed to understand the morphological, transcriptional, cell cycle and stemness based changes of stem cells in nutrient deprived medium. Our results suggest that stem cells in nutrient deprived media undergo low proliferation, high apoptosis and changed the differentiation potential of the stem cells. Serum deprived mesenchymal stem cells exhibited enhanced chondrogenic differentiation potential and reduced osteogenic differentiation potential. Moreover, the activation of key metabolic sensor AMP-activated kinase (AMPK) leads to activation of transcription factors such as FOXO3, which leads to an S phase quiescence. Serum deprivation also enhanced the expression of stemness related genes Sox2 and c-Myc.
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24
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Hariharan A, Iyer J, Wang A, Tran SD. Tracking of Oral and Craniofacial Stem Cells in Tissue Development, Regeneration, and Diseases. Curr Osteoporos Rep 2021; 19:656-668. [PMID: 34741728 DOI: 10.1007/s11914-021-00705-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/15/2021] [Indexed: 10/19/2022]
Abstract
PURPOSE OF REVIEW The craniofacial region hosts a variety of stem cells, all isolated from different sources of bone and cartilage. However, despite scientific advancements, their role in tissue development and regeneration is not entirely understood. The goal of this review is to discuss recent advances in stem cell tracking methods and how these can be advantageously used to understand oro-facial tissue development and regeneration. RECENT FINDINGS Stem cell tracking methods have gained importance in recent times, mainly with the introduction of several molecular imaging techniques, like optical imaging, computed tomography, magnetic resonance imaging, and ultrasound. Labelling of stem cells, assisted by these imaging techniques, has proven to be useful in establishing stem cell lineage for regenerative therapy of the oro-facial tissue complex. Novel labelling methods complementing imaging techniques have been pivotal in understanding craniofacial tissue development and regeneration. These stem cell tracking methods have the potential to facilitate the development of innovative cell-based therapies.
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Affiliation(s)
- Arvind Hariharan
- McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, 3640 University Street, Montreal, QC, H3A 0C7, Canada
| | - Janaki Iyer
- McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, 3640 University Street, Montreal, QC, H3A 0C7, Canada
| | - Athena Wang
- McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, 3640 University Street, Montreal, QC, H3A 0C7, Canada
| | - Simon D Tran
- McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, 3640 University Street, Montreal, QC, H3A 0C7, Canada.
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25
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Shang L, Shao J, Ge S. Immunomodulatory functions of oral mesenchymal stem cells: Novel force for tissue regeneration and disease therapy. J Leukoc Biol 2021; 110:539-552. [PMID: 34184321 DOI: 10.1002/jlb.3mr0321-766r] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Indexed: 12/16/2022] Open
Abstract
Mesenchymal stem cells (MSCs)-based therapeutic strategies have achieved remarkable efficacies. Oral tissue-derived MSCs, with powerful self-renewal and multilineage differentiation abilities, possess the features of abundant sources and easy accessibility and hold great potential in tissue regeneration and disease therapies. Oral MSCs mainly consist of periodontal ligament stem cells, gingival mesenchymal stem cells, dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from the apical papilla, dental follicle stem cells, and alveolar bone-derived mesenchymal stem. Early immunoinflammatory response stage is the prerequisite phase of healing process. Besides the potent capacities of differentiation and regeneration, oral MSCs are capable of interacting with various immune cells and function as immunomodulatory regulators. Consequently, the immunomodulatory effects of oral MSCs during damage repair seem to be crucial for exploring novel immunomodulatory strategies to achieve disease recovery and tissue regeneration. Herein, we reviewed various oral MSCs with their immunomodulatory properties and the potential mechanism, as well as their effects on immunomodulation-mediated disease therapies and tissue regeneration.
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Affiliation(s)
- Lingling Shang
- Department of Periodontology, School and Hospital of Stomatology, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China
| | - Jinlong Shao
- Department of Periodontology, School and Hospital of Stomatology, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China
| | - Shaohua Ge
- Department of Periodontology, School and Hospital of Stomatology, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China
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Soudi A, Yazdanian M, Ranjbar R, Tebyanian H, Yazdanian A, Tahmasebi E, Keshvad A, Seifalian A. Role and application of stem cells in dental regeneration: A comprehensive overview. EXCLI JOURNAL 2021; 20:454-489. [PMID: 33746673 PMCID: PMC7975587 DOI: 10.17179/excli2021-3335] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 02/09/2021] [Indexed: 12/18/2022]
Abstract
Recently, a growing attention has been observed toward potential advantages of stem cell (SC)-based therapies in regenerative treatments. Mesenchymal stem/stromal cells (MSCs) are now considered excellent candidates for tissue replacement therapies and tissue engineering. Autologous MSCs importantly contribute to the state-of-the-art clinical strategies for SC-based alveolar bone regeneration. The donor cells and immune cells play a prominent role in determining the clinical success of MSCs therapy. In line with the promising future that stem cell therapy has shown for tissue engineering applications, dental stem cells have also attracted the attention of the relevant researchers in recent years. The current literature review aims to survey the variety and extension of SC-application in tissue-regenerative dentistry. In this regard, the relevant English written literature was searched using keywords: "tissue engineering", "stem cells", "dental stem cells", and "dentistry strategies". According to the available database, SCs application has become increasingly widespread because of its accessibility, plasticity, and high proliferative ability. Among the growing recognized niches and tissues containing higher SCs, dental tissues are evidenced to be rich sources of MSCs. According to the literature, dental SCs are mostly present in the dental pulp, periodontal ligament, and dental follicle tissues. In this regard, the present review has described the recent findings on the potential of dental stem cells to be used in tissue regeneration.
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Affiliation(s)
- Armin Soudi
- Research Center for Prevention of Oral and Dental Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mohsen Yazdanian
- Research Center for Prevention of Oral and Dental Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Reza Ranjbar
- Research Center for Prevention of Oral and Dental Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Hamid Tebyanian
- Research Center for Prevention of Oral and Dental Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Alireza Yazdanian
- Department of Veterinary, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Elahe Tahmasebi
- Research Center for Prevention of Oral and Dental Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Ali Keshvad
- Research Center for Prevention of Oral and Dental Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Alexander Seifalian
- Nanotechnology and Regenerative Medicine Commercialization Centre (Ltd), The London Bioscience Innovation Centre, London, UK
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Angiogenesis in Regenerative Dentistry: Are We Far Enough for Therapy? Int J Mol Sci 2021; 22:ijms22020929. [PMID: 33477745 PMCID: PMC7832295 DOI: 10.3390/ijms22020929] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Revised: 01/14/2021] [Accepted: 01/15/2021] [Indexed: 12/14/2022] Open
Abstract
Angiogenesis is a broad spread term of high interest in regenerative medicine and tissue engineering including the dental field. In the last two decades, researchers worldwide struggled to find the best ways to accelerate healing, stimulate soft, and hard tissue remodeling. Stem cells, growth factors, pathways, signals, receptors, genetics are just a few words that describe this area in medicine. Dental implants, bone and soft tissue regeneration using autologous grafts, or xenografts, allografts, their integration and acceptance rely on their material properties. However, the host response, through its vascularization, plays a significant role. The present paper aims to analyze and organize the latest information about the available dental stem cells, the types of growth factors with pro-angiogenic effect and the possible therapeutic effect of enhanced angiogenesis in regenerative dentistry.
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Gholami L, Nooshabadi VT, Shahabi S, Jazayeri M, Tarzemany R, Afsartala Z, Khorsandi K. Extracellular vesicles in bone and periodontal regeneration: current and potential therapeutic applications. Cell Biosci 2021; 11:16. [PMID: 33436061 PMCID: PMC7802187 DOI: 10.1186/s13578-020-00527-8] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 12/31/2020] [Indexed: 12/12/2022] Open
Abstract
Oral mesenchymal stem cells (MSCs) and their secretomes are considered important factors in the field of medical tissue engineering and cell free biotherapy due to their ease of access, differentiation potential, and successful therapeutic outcomes. Extracellular vesicles (EVs) and the conditioned medium (CM) from MSCs are gaining more attraction as an alternative to cell-based therapies due to the less ethical issues involved, and their easier acquisition, preservation, long term storage, sterilization, and packaging. Bone and periodontal regenerative ability of EVs and CM have been the focus of some recent studies. In this review, we looked through currently available literature regarding MSCs' EVs or conditioned medium and their general characteristics, function, and regenerative potentials. We will also review the novel applications in regenerating bone and periodontal defects.
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Affiliation(s)
- Leila Gholami
- Department of Periodontics, Dental Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Vajihe Taghdiri Nooshabadi
- Department of Tissue Engineering and Applied Cell Sciences, School of Medicine, Semnan University of Medical Science, Semnan, Iran
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | - Shiva Shahabi
- Student Research Committee, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Marzieh Jazayeri
- Student Research Committee, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Rana Tarzemany
- Department of Oral Biological and Medical Sciences, Faculty of Dentistry, The University of British Columbia, Vancouver, Canada
| | - Zohreh Afsartala
- Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Science, Tehran, Iran
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Khatereh Khorsandi
- Department of Photodynamic, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran.
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Zhou YK, Zhu LS, Huang HM, Cui SJ, Zhang T, Zhou YH, Yang RL. Stem cells from human exfoliated deciduous teeth ameliorate concanavalin A-induced autoimmune hepatitis by protecting hepatocytes from apoptosis. World J Stem Cells 2020; 12:1623-1639. [PMID: 33505604 PMCID: PMC7789126 DOI: 10.4252/wjsc.v12.i12.1623] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 09/20/2020] [Accepted: 10/12/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Autoimmune hepatitis is a serious autoimmune liver disease that threatens human health worldwide, which emphasizes the urgent need to identify novel treatments. Stem cells from human exfoliated deciduous teeth (SHED), which are easy to obtain in a non-invasive manner, show pronounced proliferative and immunomodulatory capacities.
AIM To investigate the protective effects of SHED on concanavalin A (ConA)-induced hepatitis in mice, and to elucidate the associated regulatory mechanisms.
METHODS We used a ConA-induced acute hepatitis mouse model and an in vitro co-culture system to study the protective effects of SHED on ConA-induced autoimmune hepatitis, as well as the associated underlying mechanisms.
RESULTS SHED infusion could prevent aberrant histopathological liver architecture caused by ConA-induced infiltration of CD3+, CD4+, tumor necrosis-alpha+, and interferon-gamma+ inflammatory cells. Alanine aminotransferase and aspartate aminotransferase were significantly elevated in hepatitis mice. SHED infusion could therefore block ConA-induced alanine aminotransferase and aspartate aminotransferase elevations. Mechanistically, ConA upregulated tumor necrosis-alpha and interferon-gamma expression, which was activated by the nuclear factor-kappa B pathway to induce hepatocyte apoptosis, resulting in acute liver injury. SHED administration protected hepatocytes from ConA-induced apoptosis.
CONCLUSION SHED alleviates ConA-induced acute liver injury via inhibition of hepatocyte apoptosis mediated by the nuclear factor-kappa B pathway. Our findings could provide a potential treatment strategy for hepatitis.
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Affiliation(s)
- Yi-Kun Zhou
- Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
| | - Ling-Su Zhu
- Department of Orthodontics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Hua-Ming Huang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
| | - Sheng-Jie Cui
- Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
| | - Ting Zhang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
| | - Yan-Heng Zhou
- Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
| | - Rui-Li Yang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
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Giudice A, Antonelli A, Chiarella E, Baudi F, Barni T, Di Vito A. The Case of Medication-Related Osteonecrosis of the Jaw Addressed from a Pathogenic Point of View. Innovative Therapeutic Strategies: Focus on the Most Recent Discoveries on Oral Mesenchymal Stem Cell-Derived Exosomes. Pharmaceuticals (Basel) 2020; 13:ph13120423. [PMID: 33255626 PMCID: PMC7760182 DOI: 10.3390/ph13120423] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 11/16/2020] [Accepted: 11/23/2020] [Indexed: 02/06/2023] Open
Abstract
Bisphosphonates-related osteonecrosis of the jaw (BRONJ) was firstly reported by Marx in 2003. Since 2014, the term medication-related osteonecrosis of the jaw (MRONJ) is recommended by the American Association of Oral and Maxillofacial Surgeons (AAOMS). Development of MRONJ has been associated to the assumption of bisphosphonates but many MRONJ-promoting factors have been identified. A strong involvement of immunity components has been suggested. Therapeutic intervention includes surgical and non-surgical treatments, as well as regenerative medicine procedures for the replacement of the lost tissues. The literature confirms that the combination of mesenchymal stem cells (MSCs), biomaterials and local biomolecules can support the regeneration/repair of different structures. In this review, we report the major open topics in the pathogenesis of MRONJ. Then, we introduce the oral tissues recognized as sources of MSCs, summing up in functional terms what is known about the exosomes release in physiological and pathological conditions.
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Affiliation(s)
- Amerigo Giudice
- Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (A.G.); (A.A.)
| | - Alessandro Antonelli
- Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (A.G.); (A.A.)
| | - Emanuela Chiarella
- Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (E.C.); (F.B.); (T.B.)
| | - Francesco Baudi
- Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (E.C.); (F.B.); (T.B.)
| | - Tullio Barni
- Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (E.C.); (F.B.); (T.B.)
| | - Anna Di Vito
- Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (E.C.); (F.B.); (T.B.)
- Correspondence:
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Matichescu A, Ardelean LC, Rusu LC, Craciun D, Bratu EA, Babucea M, Leretter M. Advanced Biomaterials and Techniques for Oral Tissue Engineering and Regeneration-A Review. MATERIALS (BASEL, SWITZERLAND) 2020; 13:E5303. [PMID: 33238625 PMCID: PMC7700200 DOI: 10.3390/ma13225303] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 11/15/2020] [Accepted: 11/19/2020] [Indexed: 12/11/2022]
Abstract
The reconstruction or repair of oral and maxillofacial functionalities and aesthetics is a priority for patients affected by tooth loss, congenital defects, trauma deformities, or various dental diseases. Therefore, in dental medicine, tissue reconstruction represents a major interest in oral and maxillofacial surgery, periodontics, orthodontics, endodontics, and even daily clinical practice. The current clinical approaches involve a vast array of techniques ranging from the traditional use of tissue grafts to the most innovative regenerative procedures, such as tissue engineering. In recent decades, a wide range of both artificial and natural biomaterials and scaffolds, genes, stem cells isolated from the mouth area (dental follicle, deciduous teeth, periodontal ligament, dental pulp, salivary glands, and adipose tissue), and various growth factors have been tested in tissue engineering approaches in dentistry, with many being proven successful. However, to fully eliminate the problems of traditional bone and tissue reconstruction in dentistry, continuous research is needed. Based on a recent literature review, this paper creates a picture of current innovative strategies applying dental stem cells for tissue regeneration in different dental fields and maxillofacial surgery, and offers detailed information regarding the available scientific data and practical applications.
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Affiliation(s)
- Anamaria Matichescu
- Department of Preventive Dentistry, Community and Oral Health, “Victor Babeș” University of Medicine and Pharmacy Timisoara, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania;
| | - Lavinia Cosmina Ardelean
- Department of Technology of Materials and Devices in Dental Medicine, “Victor Babeș” University of Medicine and Pharmacy Timisoara, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania
| | - Laura-Cristina Rusu
- Department of Oral Pathology, “Victor Babeș” University of Medicine and Pharmacy Timisoara, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania; (L.-C.R.); (D.C.); (M.B.)
| | - Dragos Craciun
- Department of Oral Pathology, “Victor Babeș” University of Medicine and Pharmacy Timisoara, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania; (L.-C.R.); (D.C.); (M.B.)
| | - Emanuel Adrian Bratu
- Department of Implant Supported Restorations, “Victor Babeș” University of Medicine and Pharmacy Timisoara, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania
| | - Marius Babucea
- Department of Oral Pathology, “Victor Babeș” University of Medicine and Pharmacy Timisoara, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania; (L.-C.R.); (D.C.); (M.B.)
| | - Marius Leretter
- Department of Prosthodontics, “Victor Babeș” University of Medicine and Pharmacy Timisoara, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania;
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Potential Therapeutic Effects of Exosomes in Regenerative Endodontics. Arch Oral Biol 2020; 120:104946. [PMID: 33129129 DOI: 10.1016/j.archoralbio.2020.104946] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 09/07/2020] [Accepted: 10/04/2020] [Indexed: 02/05/2023]
Abstract
OBJECTIVE This review aims to describe the basic characteristics of exosomes, and summarize their possible source and potential biological effects in pulp regeneration, providing new insights into the therapeutic role of exosomes for regenerative endodontics in the future. DESIGN A comprehensive review of scientific literature related to exosomes potentially used for pulp regeneration was conducted. RESULTS Dental mesenchymal stem cells (MSCs) play an important role in dental pulp regeneration. MSC-derived exosomes, as important biotransmitters in intercellular communication, have been shown to replicate the therapeutic effects of their parental cells. These exosomes have better stability, lower immunogenicity, higher safety and clinical efficiency, making it possible to apply them in pulp regeneration. Existing research suggests that exosomes could trigger the regeneration of dentin/pulp-like tissue in vivo, which may attribute to their role in promoting pulp angiogenesis, regulating dental cell proliferation, migration and differentiation, and providing neuroprotection. CONCLUSIONS The applications of exosomes in the treatment of pulp regeneration have great potential, and exosomes may become ideal therapeutic biomaterial in regenerative endodontics.
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Guo H, Zhao W, Liu A, Wu M, Shuai Y, Li B, Huang X, Liu X, Yang X, Guo X, Xuan K, Jin Y. SHED promote angiogenesis in stem cell-mediated dental pulp regeneration. Biochem Biophys Res Commun 2020; 529:1158-1164. [PMID: 32819580 DOI: 10.1016/j.bbrc.2020.06.151] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Accepted: 06/26/2020] [Indexed: 01/01/2023]
Abstract
Dental pulp, plays an indispensable role in maintaining homeostasis of the tooth. Pulp necrosis always causes tooth nutrition deficiency and abnormal root development, which leads to tooth discoloration, fracture or even loss. Our previous study showed implantation of autologous SHED could regenerate functional dental pulp. However, the detailed mechanism of the implanted SHED participating in dental pulp regeneration remains unknown. In this study, we implanted SHED in a porcine dental pulp regeneration model to evaluate the regenerative effect and identify whether SHED promoted angiogenesis in regenerated dental pulp. Firstly we verified that xenogenous SHED had the ability to regenerated pulp tissue of host in vivo. Then we found the vasculature in regenerated pulp originated from implanted SHED. In addition, stem cells were isolated from regenerated dental pulp, which exhibited good multi-differentiation properties and promoted angiogenesis in pulp regeneration process and these results demonstrated that SHED promoted angiogenesis in stem cell-mediated dental pulp regeneration.
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Affiliation(s)
- Hao Guo
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, China; Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China
| | - Wanmin Zhao
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, China
| | - Anqi Liu
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, China
| | - Meiling Wu
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, China; Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China
| | - Yi Shuai
- Department of Stomatology, General Hospital of Eastern Theater Command, PLA, Nanjing, China
| | - Bei Li
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, China
| | - Xiaoyao Huang
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, China; Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China
| | - Xuemei Liu
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, China; Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China
| | - Xiaoxue Yang
- Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China
| | - Xiaohe Guo
- Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China
| | - Kun Xuan
- Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
| | - Yan Jin
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
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Zalaf BR, Bringel M, Jorge PK, de Oliveira B, Tanabe K, Santos CF, Oliveira RC, Rios D, Cruvinel T, Lourenço Neto N, Oliveira TM, Machado MAAM. A Biobank of Stem Cells of Human Exfoliated Deciduous Teeth: Overview of Applications and Developments in Brazil. Cells Tissues Organs 2020; 209:37-42. [PMID: 32541141 DOI: 10.1159/000506677] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 02/17/2020] [Indexed: 11/19/2022] Open
Abstract
A biobank is an organized collection of biological human material and its associated information stored for research according to regulations under institutional responsibility, without commercial purposes, being a mandatory and strategical activity for research, regenerative medicine, and innovation. Stem cells have largely been employed in research and frequently stored in biobanks, which have been used as an essential source of biological materials. Stem cells of human exfoliated deciduous teeth (SHED) are stem cells which have a high multipotency and can be easily obtained. Besides, this extremely accessible tissue has advantages with respect to storage, as the SHED obtained in childhood can be used in later life, which implies the necessity for the creation and regulation of biobanks. The proper planning for the creation of a biobank includes knowledge of the material types to be stored, requirements regarding handling and storage conditions, storage time, and room for the number of samples. Thus, this study aimed to establish an overview of the development of a SHED biobank. Ethical and legal standardization, current applications, specific orientations, and challenges for the implementation of a SHED biobank were discussed. Through this overview, we hope to encourage further studies to use SHED biobanks.
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Affiliation(s)
- Bianca Rapini Zalaf
- Department of Pediatric Dentistry, Orthodontics, and Public Health, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil,
| | - Mayara Bringel
- Department of Pediatric Dentistry, Orthodontics, and Public Health, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil
| | - Paula Karine Jorge
- Department of Pediatric Dentistry, Orthodontics, and Public Health, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil
| | - Bárbara de Oliveira
- Department of Pediatric Dentistry, Orthodontics, and Public Health, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil
| | - Kim Tanabe
- Department of Pediatric Dentistry, Orthodontics, and Public Health, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil
| | - Carlos Ferreira Santos
- Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil
| | - Rodrigo Cardoso Oliveira
- Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil
| | - Daniela Rios
- Department of Pediatric Dentistry, Orthodontics, and Public Health, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil
| | - Thiago Cruvinel
- Department of Pediatric Dentistry, Orthodontics, and Public Health, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil
| | - Natalino Lourenço Neto
- Department of Pediatric Dentistry, Orthodontics, and Public Health, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil
| | - Thais Marchini Oliveira
- Department of Pediatric Dentistry, Orthodontics, and Public Health, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil
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Sousa MGDC, Xavier PD, Lima SMDF, Almeida JAD, Franco OL, Rezende TMB. Enterococcus faecalis and Staphylococcus aureus stimulate nitric oxide production in macrophages and fibroblasts in vitro. BRAZILIAN JOURNAL OF ORAL SCIENCES 2020. [DOI: 10.20396/bjos.v19i0.8657039] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
Aim: Nitric oxide (NO) is an important mediator related to damage of the pulp tissue and at the same time to regenerative pulp processes. However, it is not clear how common endodontic microorganisms can regulate this mediator. This study aimed to investigate NO production by macrophages and fibroblasts against Enterococcus faecalis- and Staphylococcus aureus-antigens. Methods: RAW 264.7 macrophages and L929 fibroblast cell lines were stimulated with different heat-killed (HK) antigen concentrations (105-108 colony forming units - CFU) from E. faecalis and S. aureus with or without interferon-gamma (IFN-γ). Cell viability by MTT colorimetric assay and NO production from the culture supernatants were evaluated after 72 h. Results: Data here reported demonstrated that none of the antigen concentrations decreased cell viability in macrophages and fibroblasts. The presence of HK-S. aureus and HK-E. faecalis antigen- stimulated NO production with or without IFN-γ on RAW 264.7. The HK-S. aureus antigen stimulated NO production in L929 fibroblasts with or without IFN-γ, and the highest concentration of HK-E. faecalis with IFN-γ also stimulated NO production by these cells. Conclusion: The amount of NO produced by macrophages and fibroblasts may be involved in the concentration and type of prevalent endodontic microorganisms, generating new answers for the understanding of pulpal revascularization/regeneration processes.
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Transplantation of Stem Cells from Human Exfoliated Deciduous Teeth Decreases Cognitive Impairment from Chronic Cerebral Ischemia by Reducing Neuronal Apoptosis in Rats. Stem Cells Int 2020; 2020:6393075. [PMID: 32215019 PMCID: PMC7079222 DOI: 10.1155/2020/6393075] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 01/24/2020] [Accepted: 02/05/2020] [Indexed: 02/08/2023] Open
Abstract
Stem cells from human exfoliated deciduous teeth (SHED) are a unique postnatal stem cell population with high self-renewal ability that originates from the cranial neural crest. Since SHED are homologous to the central nervous system, they possess superior capacity to differentiate into neural cells. However, whether and how SHED ameliorate degenerative central nervous disease are unclear. Chronic cerebral ischemia (CCI) is a kind of neurological disease caused by long-term cerebral circulation insufficiency and is characterized by progressive cognitive and behavioral deterioration. In this study, we showed that either systemic transplantation of SHED or SHED infusion into the hippocampus ameliorated cognitive impairment of CCI rats in four weeks after SHED treatment by rescuing the number of neurons in the hippocampus area. Mechanistically, SHED transplantation decreased the apoptosis of neuronal cells in the hippocampus area of CCI rats through downregulation of cleaved caspase-3. In summary, SHED transplantation protected the neuronal function and reduced neuronal apoptosis, resulting in amelioration of cognitive impairment from CCI. Our findings suggest that SHED are a promising stem cell source for cell therapy of neurological diseases in the clinic.
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Alomar RK, Aladhyani SM, Aldossary MN, Almohaimel SA, Salam M, Almutairi AF. A prospective Saudi dental stem-cell bank from the perspective of the public and dental practitioners: A cross sectional survey. J Family Med Prim Care 2020; 9:864-870. [PMID: 32318436 PMCID: PMC7113985 DOI: 10.4103/jfmpc.jfmpc_978_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 12/28/2019] [Accepted: 01/10/2020] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVES The aim of this study (1) To evaluate the Saudi public's knowledge and attitude on dental stem cells (DSC) for therapeutic/banking purposes, (2) To evaluate the perception of Saudi dentists towards DSC and their attitude towards banking of DSC. METHODOLOGY This was a cross-sectional study based on an electronic survey distributed through the social media nationwide among the Saudi public, and through paper-based surveys among dentists in Riyadh. By convenience, eligible study participants were Saudi adults from the community and dentists from 17 dental centers in different regions of Riyadh. Using SPSS v. 25, descriptive statistics (n,%; PMS ± SD) and bivariate analyses (Pearson's Chi square, Mann Whitney) were conducted to determine factors associated with the study outcomes, with a P value statistically significant at <0.05. RESULTS For the Saudi public, 1494 participants completed the survey. The PMS ± SD of public knowledge was 25.5 ± 25.9, while their attitude was 80.2 ± 27.0. Factors associated with higher knowledge scores were younger age groups, while female participants, older age groups, university educated and employed participants had higher attitude. For Saudi dentists, 246/262 (94%) dentists responded to the questionnaire. Their PMS ± SD of perception towards DSC research for regenerative purposes was 74.5 ± 15.6. Factors associated with higher perception scores were those with more experience. Dentists who had higher perception scores towards DSCs were significantly more willing to save teeth for regenerative dental treatment. CONCLUSION The Saudi public community had poor knowledge about the therapeutic and research benefits of DSC, yet high degree of attitude to enroll in a future Saudi DSC bank. Saudi dentists had moderately high levels of perception towards DSC research.
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Affiliation(s)
- Rasha K. Alomar
- Preventive Dental Science, College of Dentistry, King Saud Bin Abdulaziz University of Health Sciences, Riyadh, Saudi Arabia
| | - Shahad M. Aladhyani
- College of Dentistry, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Munirah N. Aldossary
- College of Dentistry, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | | | | | - Adel F. Almutairi
- PhD. King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University of Health Sciences, Riyadh, Saudi Arabia
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Yang S, Xin C, Zhang B, Zhang H, Hao Y. Synergistic effects of Rho kinase inhibitor Y-27632 and Noggin overexpression on the proliferation and neuron-like cell differentiation of stem cells derived from human exfoliated deciduous teeth. IUBMB Life 2019; 72:665-676. [PMID: 31889420 DOI: 10.1002/iub.2208] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Accepted: 11/22/2019] [Indexed: 12/22/2022]
Abstract
Stem cells from human exfoliated deciduous teeth (SHEDs) are highly proliferative, clonogenic, and multipotent stem cells with a neural crest cell origin. This property could be a desirable option for potential therapeutic applications. In this study, we focus on the effects of Rho kinase inhibitors Y-27632 and Noggin on the proliferation of SHEDs and their differentiation into neuron-like cells. SHEDs were extracted from 10 samples of deciduous teeth obtained from healthy children aged from 5 to 10. The passaged SHEDs were transfected with Noggin, Y-27632, or their combination. By means of MTT and colony formation assays, the effects of Y-27632 and Noggin on cell viability and colony formation were detected. Cellular morphology and neurosphere formation were observed under a microscope. Y-27632 transfection in SHEDs showed enhanced cell viability, colony formation, and neurosphere formation indicating that Y-27632 could promote cell proliferation of SHEDs. Furthermore, we observed that the SHEDs treated with Noggin in combination with Y-27632 displayed typical neuron-like cell morphology and reticular processes. Noggin or Y-27632 alone or in combination induced obviously increased NSE, Nestin, and GFAP levels, which were highest in SHEDs treated with the combination of Noggin and Y-27632. These findings suggest that Y-27632 promotes the proliferation of SHEDs, and Y-27632 and Noggin in combination have a synergistic effect on promoting differentiation of SHEDs into neuron-like cells.
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Affiliation(s)
- Si Yang
- Department of Pediatric Neurology, The First Hospital of Jilin University, Changchun, China
| | - Cuijuan Xin
- Department of Pediatric Neurology, The First Hospital of Jilin University, Changchun, China
| | - Bo Zhang
- Department of Pediatric Neurology, The First Hospital of Jilin University, Changchun, China
| | - Hongbo Zhang
- Department of Pediatric Neurology, The First Hospital of Jilin University, Changchun, China
| | - Yunpeng Hao
- Department of Pediatric Neurology, The First Hospital of Jilin University, Changchun, China
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Vitor LLR, Prado MTO, Lourenço Neto N, Oliveira RC, Sakai VT, Santos CF, Dionísio TJ, Rios D, Cruvinel T, Machado MAAM, Oliveira TM. Does photobiomodulation change the synthesis and secretion of angiogenic proteins by different pulp cell lineages? JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2019; 203:111738. [PMID: 31954290 DOI: 10.1016/j.jphotobiol.2019.111738] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2019] [Revised: 09/02/2019] [Accepted: 12/09/2019] [Indexed: 12/28/2022]
Abstract
This study aimed to compare the synthesis and secretion of VEGF-A, VEGF-C, VEGF-D, VEGFR1, VEGFR2, and FGF-2 between pulp fibroblasts from human primary teeth (HPF) and stem cell from human deciduous teeth (SHED) before and after photobiomodulation. HPF were obtained from explant technique and characterized by immunohistochemistry, while SHED were obtained from digestion technique and characterized by flow cytometry. HPF (control group) and SHED were plated, let to adhere, and put on serum starvation to synchronize the cell cycles prior to photobiomodulation. Then, both cell lineages were irradiated with 660-nm laser according to the following groups: 2.5 and 3.7 J/cm2. MTT and crystal violet assays respectively verified viability and proliferation. ELISA Multiplex Assay assessed the following proteins: VEGF-A, VEGF-C, VEGF-D, VEGFR1, VEGFR2, FGF-2, at 6, 12, and 24 h after photobiomodulation, in supernatant and lysate. Two-way ANOVA/Tukey test evaluated cell viability and proliferation, while angiogenic production and secretion values were analyzed by one-way ANOVA (P < .05). Statistically similar HPF and SHED viability and proliferation patterns occurred before and after photobiomodulation (P > .05). HPF exhibited statistically greater values of all angiogenic proteins than did SHED, at all study periods, except for FGF-2 (supernatant; 12 h); VEGFR1 (lysate; non-irradiated; 12 h); and VEGFR1 (lysate; non-irradiated; 24 h). Photobiomodulation changed the synthesis and secretion of angiogenic proteins by HPF. HPF produced and secreted greater values of all tested angiogenic proteins than did SHED before and after irradiation with both energy densities of 2.5 and 3.7 J/cm2.
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Affiliation(s)
| | - Mariel Tavares Oliveira Prado
- Department of Pediatric Dentistry, Orthodontics, and Public Health, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil
| | - Natalino Lourenço Neto
- Department of Pediatric Dentistry, Orthodontics, and Public Health, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil
| | - Rodrigo Cardoso Oliveira
- Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil
| | - Vivien Thiemy Sakai
- Department of Clinics and Surgery, School of Dentistry, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil
| | - Carlos Ferreira Santos
- Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil
| | - Thiago José Dionísio
- Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil
| | - Daniela Rios
- Department of Pediatric Dentistry, Orthodontics, and Public Health, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil
| | - Thiago Cruvinel
- Department of Pediatric Dentistry, Orthodontics, and Public Health, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil
| | | | - Thais Marchini Oliveira
- Department of Pediatric Dentistry, Orthodontics, and Public Health, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.
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Wang M, Li J, Ye Y, He S, Song J. SHED-derived conditioned exosomes enhance the osteogenic differentiation of PDLSCs via Wnt and BMP signaling in vitro. Differentiation 2019; 111:1-11. [PMID: 31630077 DOI: 10.1016/j.diff.2019.10.003] [Citation(s) in RCA: 96] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Revised: 09/30/2019] [Accepted: 10/10/2019] [Indexed: 12/18/2022]
Abstract
The exosomes from human exfoliated deciduous teeth (SHED-Exos) have exhibited potential therapeutic role in dental and oral disorders. The biological effects of exosomes largely depend on cellular origin and physiological status of donor cell. In the present study, we explored the influence of conditioned exosomes from SHED with osteogenic induction on periodontal ligament stem cells (PDLSCs) in vitro. Conditioned SHED-Exos from a 3-day osteogenic supernatant were applied during PDLSCs osteogenic differentiation. We found that conditioned SHED-Exos had no cytotoxicity on PDLSCs viability assessed by CCK-8 assay. These SHED-Exos promoted PDLSCs osteogenic differentiation with deep Alizarin red staining, high alkaline phosphatase (ALP) activity and upregulated osteogenic gene expression (RUNX2, OPN and OCN). We further found BMP/Smad signaling and Wnt/β-catenin were activated by enhanced Smad1/5/8 phosphorylation and increased nuclear β-catenin protein expression. Inhibiting these two signaling pathways with specific inhibitors (cardamonin and LDN193189) remarkably weakened the enhanced osteogenic differentiation. Furthermore, Wnt3a and BMP2 were upregulated in SHED and SHED-Exos. Silencing Wnt3a and BMP2 in SHED-Exos partially counteracts the enhanced osteogenic differentiation. Our findings indicate that conditioned SHED-Exos-enhanced PDLSCs osteogenic differentiation was partly due to its carrying Wnt3a and BMP2. These data provide new insights into the use of SHED-Exos in periodontitis-induced bone defects therapy.
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Affiliation(s)
- Menghong Wang
- College of Stomatology, Chongqing Medical University, 426 Songshibei Road, Chongqing, 401147, PR China; Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, 426 Songshibei Road, Chongqing, 401147, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, 426 Songshibei Road, Chongqing, 401147, PR China
| | - Jie Li
- College of Stomatology, Chongqing Medical University, 426 Songshibei Road, Chongqing, 401147, PR China; Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, 426 Songshibei Road, Chongqing, 401147, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, 426 Songshibei Road, Chongqing, 401147, PR China
| | - Yanyan Ye
- Department of Stomatology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, PR China
| | - Songlin He
- College of Stomatology, Chongqing Medical University, 426 Songshibei Road, Chongqing, 401147, PR China; Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, 426 Songshibei Road, Chongqing, 401147, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, 426 Songshibei Road, Chongqing, 401147, PR China.
| | - Jinlin Song
- College of Stomatology, Chongqing Medical University, 426 Songshibei Road, Chongqing, 401147, PR China; Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, 426 Songshibei Road, Chongqing, 401147, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, 426 Songshibei Road, Chongqing, 401147, PR China.
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piggyBac Transposon-Based Immortalization of Human Deciduous Tooth Dental Pulp Cells with Multipotency and Non-Tumorigenic Potential. Int J Mol Sci 2019; 20:ijms20194904. [PMID: 31623314 PMCID: PMC6801629 DOI: 10.3390/ijms20194904] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2019] [Revised: 09/21/2019] [Accepted: 09/30/2019] [Indexed: 12/14/2022] Open
Abstract
We aimed to immortalize primarily isolated human deciduous tooth-derived dental pulp cells (HDDPCs) by transfection with piggyBac (PB)-based transposon vectors carrying E7 from human papilloma virus 16 or complementary DNA (cDNA) encoding human telomerase reverse transcriptase (hTERT). HDDPCs were co-transfected with pTrans (conferring PB transposase expression) + pT-pac (conferring puromycin acetyltransferase expression) + pT-tdTomato (conferring tdTomato cDNA expression) and pT-E7 (conferring E7 expression) or pTrans + pT-pac + pT-EGFP (conferring enhanced green fluorescent protein cDNA expression) + pT-hTERT (conferring hTERT expression). After six days, these cells were selected in medium containing 5 μg/mL puromycin for one day, and then cultured in normal medium allowing cell survival. All resultant colonies were harvested and propagated as a pool. Stemness and tumorigenic properties of the established cell lines (“MT_E7” for E7 and “MT_hTERT” for hTERT) with untransfected parental cells (MT) were examined. Both lines exhibited proliferation similar to that of MT, with alkaline phosphatase activity and stemness-specific factor expression. They displayed differentiation potential into multi-lineage cells with no tumorigenic property. Overall, we successfully obtained HDDPC-derived immortalized cell lines using a PB-based transfection system. The resultant and parental cells were indistinguishable. Thus, E7 and hTERT could immortalize HDDPCs without causing cancer-associated changes or altering phenotypic properties.
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Wu J, Chen L, Wang R, Song Z, Shen Z, Zhao Y, Huang S, Lin Z. Exosomes Secreted by Stem Cells from Human Exfoliated Deciduous Teeth Promote Alveolar Bone Defect Repair through the Regulation of Angiogenesis and Osteogenesis. ACS Biomater Sci Eng 2019; 5:3561-3571. [PMID: 33405738 DOI: 10.1021/acsbiomaterials.9b00607] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Jinyan Wu
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, No. 56, Lingyuan West Road, Guangzhou 510055, China
| | - Lingling Chen
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, No. 56, Lingyuan West Road, Guangzhou 510055, China
| | - Runfu Wang
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, No. 56, Lingyuan West Road, Guangzhou 510055, China
| | - Zhi Song
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, No. 56, Lingyuan West Road, Guangzhou 510055, China
| | - Zongshan Shen
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, No. 56, Lingyuan West Road, Guangzhou 510055, China
| | - Yiming Zhao
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, No. 56, Lingyuan West Road, Guangzhou 510055, China
| | - Shuheng Huang
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, No. 56, Lingyuan West Road, Guangzhou 510055, China
| | - Zhengmei Lin
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, No. 56, Lingyuan West Road, Guangzhou 510055, China
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Oxidative Stress-Tolerant Stem Cells from Human Exfoliated Deciduous Teeth Decrease Hydrogen Peroxide-Induced Damage in Organotypic Brain Slice Cultures from Adult Mice. Int J Mol Sci 2019; 20:ijms20081858. [PMID: 30991705 PMCID: PMC6514841 DOI: 10.3390/ijms20081858] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 04/11/2019] [Accepted: 04/12/2019] [Indexed: 02/08/2023] Open
Abstract
Oxidative stress causes severe tissue injury of the central nervous system in ischemic brain damage (IBD), traumatic brain injury (TBI) and neurodegenerative disorders. In this study, we used hydrogen peroxide (H₂O₂) to induce oxidative stress in organotypic brain slice cultures (OBSCs), and investigated the protective effects of oxidative stress-tolerant (OST) stem cells harvested from human exfoliated deciduous teeth (SHED) which were co-cultivated with OBSCs. Using presto blue assay and immunostaining, we demonstrated that both normal SHED and OST-SHED could prevent H₂O₂-induced cell death, and increase the numbers of mature neuron and neuronal progenitors in the hippocampus of OBSCs. During co-cultivation, OST-SHED, but not normal SHED, exhibited neuronal cell morphology and expressed neuronal markers. Results from ELISA showed that both normal SHED and OST-SHED significantly decreased oxidative DNA damage in H₂O₂-treated OBSCs. SHED could also produce neurotrophic factor BDNF (brain derived neurotrophic factor) and promoted the production of IL-6 in OBSCs. Although OST-SHED had lower cell viability, the neuronal protection of OST-SHED was significantly superior to that of normal SHED. Our findings suggest that SHED, especially OST-SHED, could prevent oxidative stress induced brain damage. OST-SHED can be explored as a new therapeutic tool for IBD, TBI and neurodegenerative disorders.
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Yang X, Ma Y, Guo W, Yang B, Tian W. Stem cells from human exfoliated deciduous teeth as an alternative cell source in bio-root regeneration. Am J Cancer Res 2019; 9:2694-2711. [PMID: 31131062 PMCID: PMC6525984 DOI: 10.7150/thno.31801] [Citation(s) in RCA: 72] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 03/25/2019] [Indexed: 02/05/2023] Open
Abstract
A stem cell-mediated bioengineered tooth root (bio-root) has proven to be a prospective tool for the treatment of tooth loss. As shown in our previous studies, dental follicle cells (DFCs) are suitable seeding cells for the construction of bio-roots. However, the DFCs which can only be obtained from unerupted tooth germ are restricted. Stem cells from human exfoliated deciduous teeth (SHEDs), which are harvested much more easily through a minimally invasive procedure, may be used as an alternative seeding cell. In this case, we compared the odontogenic characteristics of DFCs and SHEDs in bio-root regeneration. Methods: The biological characteristics of SHEDs and DFCs were determined in vitro. The cells were then induced to secrete abundant extracellular matrix (ECM) and form macroscopic cell sheets. We combined the cell sheets with treated dentin matrix (TDM) for subcutaneous transplantation into nude mice and orthotopic jaw bone implantation in Sprague-Dawley rats to further verify their regenerative potential. Results: DFCs exhibited a higher proliferation rate and stronger osteogenesis and adipogenesis capacities, while SHEDs displayed increased migration ability and excellent neurogenic potential. Both dental follicle cell sheets (DFCSs) and sheets of stem cells from human exfoliated deciduous teeth (SHEDSs) expressed not only ECM proteins but also osteogenic and odontogenic proteins. Importantly, similar to DFCSs/TDM, SHEDSs/TDM also successfully achieved the in vivo regeneration of the periodontal tissues, which consist of periodontal ligament fibers, blood vessels and new born alveolar bone. Conclusions: Both SHEDs and DFCs possessed a similar odontogenic differentiation capacity in vivo, and SHEDs were regarded as a prospective seeding cell for use in bio-root regeneration in the future.
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Liu J, Zhang ZY, Yu H, Yang AP, Hu PF, Liu Z, Wang M. Long noncoding RNA C21orf121/bone morphogenetic protein 2/microRNA-140-5p gene network promotes directed differentiation of stem cells from human exfoliated deciduous teeth to neuronal cells. J Cell Biochem 2019; 120:1464-1476. [PMID: 30317665 DOI: 10.1002/jcb.27313] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 06/26/2018] [Indexed: 01/24/2023]
Abstract
Previous studies have revealed that long noncoding RNA (lncRNA) and microRNA play a crucial role in autism, which is a childhood neurodevelopmental disorder with complicated genetic origins. Hence, the study concerns whether lncRNA C21orf121/bone morphogenetic proteins 2 (BMP2)/miR-140-5p gene network affects directed differentiation of stem cells from human exfoliated deciduous teeth (SHED) to neuronal cells in rats with autism. Autism models were successfully established. The neuron cells that differentiated from SHED cell were identified. The expression of lncRNA C21orf121, miR-140-5p, BMP2, Nestin, βIII-tubulin, and microtubule-associated protein 2 (MAP2) and the expression of neuron-specific enolase (NSE) were examined. Besides, the gap junction (GJ) function of SHED, the intracellular free Ca 2+ concentration, and the social behavior and repetitive stereotyped movements of rats in autism were detected. The target relationship between lncRNA C21orf121 and miR-140-5p and that between miR-140-5p and BMP2 were also verified. Firstly, we successfully isolated SHED and identified the differentiated neurons of SHED. Besides, the expression of BMP2, MAP2, Nestin, βIII-tubulin, NSE positive rate, GJ function, and intracellular free Ca 2+ concentration were increased with the upregulation of C21orf121 and downregulation of miR-140-5p, and accumulated time of repetitive stereotyped movements decreased and the frequency of social behavior increased. The results indicate that lncRNA C21orf121 as a competing endogenous RNA competes with BMP2 binding to miR-140-5p, thereby promoting SHED to differentiate into neuronal cells via upregulating BMP2 expression.
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Affiliation(s)
- Jun Liu
- Department of Clinical Laboratory, Zhejiang Xiaoshan Hospital, Hangzhou, China
| | - Zeng-Yu Zhang
- Department of Pediatrics, Xiaoshan First Affiliated Hospital of Hangzhou Normal University, Hangzhou, China
| | - Hong Yu
- Department of Child and Adolescent Mental Health, Zhejiang Xiaoshan Hospital, Hangzhou, China
| | - Ai-Ping Yang
- Department of Clinical Laboratory, Zhejiang Xiaoshan Hospital, Hangzhou, China
| | - Ping-Fang Hu
- Department of Clinical Laboratory, Zhejiang Xiaoshan Hospital, Hangzhou, China
| | - Zhuo Liu
- Department of Internal Medicine, Zhejiang Xiaoshan Hospital, Hangzhou, China
| | - Min Wang
- Department of Clinical Laboratory, Zhejiang Xiaoshan Hospital, Hangzhou, China
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Baniebrahimi G, Khanmohammadi R, Mir F. Teeth-derived stem cells: A source for cell therapy. J Cell Physiol 2018; 234:2426-2435. [PMID: 30238990 DOI: 10.1002/jcp.27270] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Accepted: 07/26/2018] [Indexed: 12/12/2022]
Abstract
Cell therapy is one of the important therapeutic approaches in the treatment of many diseases such as cancer, degenerative diseases, and cardiovascular diseases. Among various cell types, which could be used as cell therapies, stem cell therapy has emerged as powerful tools in the treatment of several diseases. Multipotent stem cells are one of the main classes of stem cells that could originate from different parts of the body such as bone marrow, adipose, placenta, and tooth. Among several types of multipotent stem cells, tooth-derived stem cells (TDSCs) are associated with special properties such as accessible, easy isolation, and low invasive, which have introduced them as a good source for using in the treatment of several diseases such as neural injuries, liver fibrosis, and Cohrn's disease. Here, we provided an overview of TDSCs particular stem cells from human exfoliated deciduous teeth and clinical application of them. Moreover, we highlighted molecular mechanisms involved in the regulation of dental stem cells fate.
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Affiliation(s)
- Ghazaleh Baniebrahimi
- Department of Pediatric Dentistry, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
| | - Razieh Khanmohammadi
- Department of Pediatric Dentistry, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Mir
- Department of Pediatric Dentistry, School of Dentistry, Zahedan University of Medical Sciences, Zahedan, Iran
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Yagi Mendoza H, Yokoyama T, Tanaka T, Ii H, Yaegaki K. Regeneration of insulin-producing islets from dental pulp stem cells using a 3D culture system. Regen Med 2018; 13:673-687. [PMID: 30028236 DOI: 10.2217/rme-2018-0074] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
AIM In this study, we aimed to establish the differentiation protocol of dental pulp stem cells (DPSCs) into pancreatic islets using a 3D structure. MATERIALS & METHODS DPSCs were differentiated in a 3D culture system using a stepwise protocol. Expression of β-cell markers, glucose-stimulated insulin secretion, and PI3K/AKT and WNT pathways were compared between monolayer-cultured pancreatic cells and islets. RESULTS Islet formation increased insulin and C-peptide production, and enhanced the expression of pancreatic markers. Glucose-dependent secretion of insulin was increased by islets. Pancreatic endocrine markers, transcriptional factors, and the PI3K/AKT and WNT pathways were also upregulated. CONCLUSION Pancreatic islets were generated from DPSCs in a 3D culture system. This system could provide novel strategies for controlling diabetes through regenerative medicine.
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Affiliation(s)
- Hiromi Yagi Mendoza
- Department of Oral Health, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi, Chiyoda ku, 102-8159 Tokyo, Japan
| | - Tomomi Yokoyama
- Department of Oral Health, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi, Chiyoda ku, 102-8159 Tokyo, Japan
| | - Tomoko Tanaka
- Department of Oral Health, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi, Chiyoda ku, 102-8159 Tokyo, Japan
| | - Hisataka Ii
- Department of Oral Health, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi, Chiyoda ku, 102-8159 Tokyo, Japan
| | - Ken Yaegaki
- Department of Oral Health, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi, Chiyoda ku, 102-8159 Tokyo, Japan
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Gao X, Shen Z, Guan M, Huang Q, Chen L, Qin W, Ge X, Chen H, Xiao Y, Lin Z. Immunomodulatory Role of Stem Cells from Human Exfoliated Deciduous Teeth on Periodontal Regeneration. Tissue Eng Part A 2018; 24:1341-1353. [PMID: 29652608 DOI: 10.1089/ten.tea.2018.0016] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Periodontitis is initiated by the infection of periodontal bacteria and subsequent tissue inflammation due to immunoreaction, eventually leading to periodontal apparatus loss. Stem cells from human exfoliated deciduous teeth (SHEDs) have exhibited beneficial characteristics in dental tissue regeneration. However, the immunomodulatory functions of SHEDs have not been elucidated in the context of periodontitis treatment. In this study, we investigated the potential immunomodulatory effects of SHEDs on experimental periodontitis and demonstrated that multidose delivery of SHEDs led to periodontal tissue regeneration. SHEDs and monocytes/macrophages were cocultured in transwell systems and SHEDs were found to be capable of promoting monocyte/macrophage conversion to CD206+ M2-like phenotype. Bioluminescence imaging (BLI) was employed to assess the survival and distribution of SHEDs after delivery in periodontal tissues in an induced periodontitis model, and BLI revealed that SHEDs survived for ∼7 days in periodontal tissues with little tissue diffusion. Then, multidose SHED delivery was applied to treat periodontitis at 7-day intervals. Results showed that mutidose SHEDs altered the cytokine expression profile in gingival crevicular fluid, reduced gum bleeding, increased new attachment of periodontal ligament, and decreased osteoclast differentiation. Micro-computed tomography analysis showed SHED administration significantly increased periodontal regeneration and alveolar bone volume, and decreased distance of cementoenamel junction to alveolar bone crest. Furthermore, an increase in the number of CD206+ M2 macrophages was observed in periodontal tissues following the delivery of SHEDs, which aligned well with the promoted conversion to CD206+ M2-like cells from monocytes/macrophages in vitro after stimulation by SHEDs. This study demonstrated in a rat periodontitis model that local delivery of SHEDs attributed to the induction of M2 macrophage polarization, reduction of periodontal tissue inflammation, and enhancement of periodontal regeneration.
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Affiliation(s)
- Xianling Gao
- 1 Guangdong Provincial Key Laboratory of Stomatology, Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University , Guangzhou, China
| | - Zongshan Shen
- 1 Guangdong Provincial Key Laboratory of Stomatology, Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University , Guangzhou, China
| | - Meiliang Guan
- 1 Guangdong Provincial Key Laboratory of Stomatology, Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University , Guangzhou, China
| | - Qiting Huang
- 1 Guangdong Provincial Key Laboratory of Stomatology, Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University , Guangzhou, China
| | - Lingling Chen
- 1 Guangdong Provincial Key Laboratory of Stomatology, Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University , Guangzhou, China
| | - Wei Qin
- 1 Guangdong Provincial Key Laboratory of Stomatology, Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University , Guangzhou, China
| | - Xiaohu Ge
- 2 Guangzhou Saliai Stem Cell Science and Technology Co. Ltd. , International Biotech Island, Guangzhou, China
| | - Haijia Chen
- 2 Guangzhou Saliai Stem Cell Science and Technology Co. Ltd. , International Biotech Island, Guangzhou, China
| | - Yin Xiao
- 3 Institute of Health and Biomedical Innovation, Queensland University of Technology , Brisbane, Australia .,4 Australia-China Centre for Tissue Engineering and Regenerative Medicine, Queensland University of Technology , Brisbane, Australia
| | - Zhengmei Lin
- 1 Guangdong Provincial Key Laboratory of Stomatology, Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University , Guangzhou, China .,4 Australia-China Centre for Tissue Engineering and Regenerative Medicine, Queensland University of Technology , Brisbane, Australia
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Abstract
Currently regeneration of tooth and periodontal damage still remains great challenge. Stem cell-based tissue engineering raised novel therapeutic strategies for tooth and periodontal repair. Stem cells for tooth and periodontal regeneration include dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), stem cells from the dental apical papilla (SCAPs), and stem cells from human exfoliated deciduous teeth (SHEDs), dental follicle stem cells (DFSCs), dental epithelial stem cells (DESCs), bone marrow mesenchymal stem cells (BMMSCs), adipose-derived stem cells (ADSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). To date, substantial advances have been made in stem cell-based tooth and periodontal regeneration, including dentin-pulp, whole tooth, bioroot and periodontal regeneration. Translational investigations have been performed such as dental stem cell banking and clinical trials. In this review, we present strategies for stem cell-based tissue engineering for tooth and periodontal repair, and the translational studies.
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Affiliation(s)
- L Hu
- Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China
| | - Y Liu
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China
| | - S Wang
- Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.,Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, Beijing, China
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