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Niazi V, Ghafouri-Fard S. Effect of hypoxia on extracellular vesicles in malignant and non-malignant conditions. Cancer Treat Res Commun 2025; 43:100924. [PMID: 40209539 DOI: 10.1016/j.ctarc.2025.100924] [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: 02/22/2025] [Revised: 03/21/2025] [Accepted: 04/04/2025] [Indexed: 04/12/2025]
Abstract
Extracellular vesicles (EVs) are produced by virtually all types of cells and can be detected in nearly all extracellular places. These particles mediate intercellular communication and transfer their cargo to the recipient cells, inducing a variety of processes in these cells through transmission of several biomolecules such as miRNAs, lncRNAs, other transcripts and a variety of proteins. It has been documented that size, quantity, and expression of biomolecules in the EVs are influenced by the level of oxygen. In fact, hypoxia can affect several cellular processes through modulation of the cargo of these vesicles. Hypoxic exosomes derived from tumor cells have several protumoral effects on the recipient cells, including enhancement of proliferation, migration, and invasion in other tumoral cells, induction of metastasis in distant organs, stimulation of angiogenesis in the endothelial cells, and modulation of macrophage polarization. Hypoxic EVs also contribute to several non-malignant diseases. This review summarizes the effect of hypoxia on EVs cargo in malignant and nonmalignant diseases of different organs.
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Affiliation(s)
- Vahid Niazi
- Stem Cell Research Center, Golestan University of Medical Science, Gorgan, Iran; School of Advanced Technologies in Medicine, Golestan University of Medical Science, Gorgan, Iran
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Khosronejad A, Arabion H, Iraji A, Mokhtarzadegan M, Daneshi SS, Asadi-Yousefabad SL, Zare S, Nowzari F, Abbaspour S, Akbarizadeh F, Aliabadi E, Amiri MA, Zarei M, Ebrahimi R, Mussin NM, Kurmanalina MA, Tanideh N, Tamadon A. Mandibular bone defect healing using polylactic acid-nano-hydroxyapatite-gelatin scaffold loaded with hesperidin and dental pulp stem cells in rat. Tissue Cell 2025; 93:102700. [PMID: 39724839 DOI: 10.1016/j.tice.2024.102700] [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: 09/11/2024] [Revised: 12/17/2024] [Accepted: 12/18/2024] [Indexed: 12/28/2024]
Abstract
Addressing mandibular defects poses a significant challenge in maxillofacial surgery. Recent advancements have led to the development of various biomimetic composite scaffolds aimed at facilitating mandibular defect reconstruction. This study aimed to assess the regenerative potential of a novel composite scaffold consisting of polylactic acid (PLA), hydroxyapatite nanoparticles (n-HA), gelatin, hesperidin, and human dental pulp stem cells (DPSCs) in a rat model of mandibular bone defect. The PLA-HA-GLA composite was synthesized using solvent casting-leaching and freeze-drying methods and subsequently treated with 11 mg of hesperidin. The physicochemical properties of the PLA-HA-GLA and PLA-HA-GLA-HIS composites were analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and thermal gravimetric analysis (TGA). Additionally, the mechanical properties and cytotoxicity of DPSCs were assessed. Subsequently, PLA-HA-GLA and PLA-HA-GLA-HIS scaffolds with or without DPSCs were implanted into mandibular bone defects in rats, followed by histopathological, histomorphometric, and cone-beam computed tomography (CBCT) evaluations after eight weeks. SEM analysis revealed the porous structure of the fabricated PLA-HA-GLA and PLA-HA-GLA-HIS composites without aggregation. FTIR and XRD analyses confirmed the presence of functional groups and elements associated with PLA, HA, GLA, and hesperidin in the composites. Although the PLA-HA-GLA-HIS composite exhibited good thermal stability, its mechanical properties decreased after the addition of hesperidin. The cell viability of DPSCs on the surface of the PLA-HA-GLA-HIS scaffolds was statistically significant compared to that of the control group. Furthermore, histopathological, histomorphometric, and radiological evaluations demonstrated that the implantation of the DPSC-loaded PLA-HA-GLA-HIS scaffold had a beneficial effect on bone tissue reconstruction in rats with mandibular defects. These findings highlight the potential of DPSC-loaded PLA-HA-GLA-HIS composite scaffolds for spongy bone tissue engineering and mandibular defect repair.
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Affiliation(s)
- Arya Khosronejad
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Shiraz University of Medical Science, Shiraz, Iran
| | - Hamidreza Arabion
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Shiraz University of Medical Science, Shiraz, Iran.
| | - Aida Iraji
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Central Research laboratory, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohamad Mokhtarzadegan
- School of Metallurgy and Materials Engineering, College of Engineering, University of Tehran, Tehran, Iran.
| | - Seyyed Sajad Daneshi
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Shahrokh Zare
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fariborz Nowzari
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Shekofeh Abbaspour
- Department of Chemical and Polymer Engineering, Faculty of Engineering, Yazd University, Yazd, Iran
| | - Fatemeh Akbarizadeh
- Department of Oral & Maxillofacial Radiology, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Ehsan Aliabadi
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Shiraz University of Medical Science, Shiraz, Iran.
| | | | - Moein Zarei
- Department of Polymer and Biomaterials Science, Faculty of Chemical Technology and Engineering, West Pomeranian University of Technology, Szczecin, Al. Piastow 45, Szczecin 71-311, Poland.
| | - Reyhaneh Ebrahimi
- Department of Periodontics, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nadiar M Mussin
- Department of Surgery No. 2, West Kazakhstan Medical University, Aktobe, Kazakhstan.
| | - Madina A Kurmanalina
- Department of Therapeutic and Prosthetic Dentistry, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
| | - Nader Tanideh
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Amin Tamadon
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Natural Sciences, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan.
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Chen Y, Guo B, Zhang Y, Bao X, Li D, Lin J. Injectable hypoxia-preconditioned human exfoliated deciduous teeth stem cells encapsulated within GelMA-AMP microspheres for bone regeneration in periodontitis. Colloids Surf B Biointerfaces 2025; 247:114452. [PMID: 39689590 DOI: 10.1016/j.colsurfb.2024.114452] [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: 09/28/2024] [Revised: 11/21/2024] [Accepted: 12/09/2024] [Indexed: 12/19/2024]
Abstract
Periodontitis, an inflammatory and infectious disease resulting from dental plaque, affects tooth-supporting tissues and interconnects with various systemic conditions. Advancing periodontal tissue regeneration stands as pivotal in periodontitis treatment. Presently, odontogenic stem cells garner substantial interest for dental pulp functional tissue regeneration. Essential to stem cell delivery success is the design of suitable drug delivery vehicles. Hence, this research introduces novel injectable antimicrobial peptide-grafted methacryloyl gelatin (GelMA-AMP) microspheres, housing hypoxia-inducible factor (HIF-1α), ensuring sustained release to stimulate osteogenic differentiation of deciduous dental pulp stem cells (SHEDs). Through in vitro co-culturing and preparation of HIF-1α@GelMA-AMP@SHED cell spheres, they were injected and transplanted into periodontal pockets for periodontitis treatment. Results display microsphere sizes averaging 93.92 ± 6.00 μm, akin to human dental pulp, showcasing commendable cytocompatibility and in vitro antibacterial properties. Additionally, GelMA-AMP microspheres carrying HIF-1α enhance cell adhesion, proliferation, and extracellular matrix protein secretion. Notably, HIF-1α@GelMA-AMP@SHED microspheres were effective in reducing periodontal inflammation in vivo and promoting vascularization and tissue regeneration in the periodontal region. Consequently, the application potential of HIF-1α@GelMA-AMP@SHED hydrogel microspheres in periodontitis treatment appears promising.
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Affiliation(s)
- Yu Chen
- Department of Stomatology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Department of Stomatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510000, China
| | - Bing Guo
- Department of Stomatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510000, China
| | - Yanqing Zhang
- Department of Stomatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510000, China
| | - Xinyu Bao
- Department of Stomatology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Dan Li
- Department of Stomatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510000, China
| | - Jun Lin
- Department of Stomatology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
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Liu Y, Ren L, Li M, Zheng B, Liu Y. The Effects of Hypoxia-Preconditioned Dental Stem Cell-Derived Secretome on Tissue Regeneration. TISSUE ENGINEERING. PART B, REVIEWS 2025; 31:44-60. [PMID: 38613806 DOI: 10.1089/ten.teb.2024.0054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/15/2024]
Abstract
Mesenchymal stroma cells derived from oral tissues are known as dental stem cells (DSCs). Owing to their unique therapeutic niche and clinical accessibility, DSCs serve as a promising treatment option for bone defects and oral tissue regeneration. DSCs exist in a hypoxic microenvironment in vivo, which is far lower than the current 20% oxygen concentration used in in vitro culture. It has been widely reported that the application of an oxygen concentration less than 5% in the culture of DSCs is beneficial for preserving stemness and promoting proliferation, migration, and paracrine activity. The paracrine function of DSCs involves the secretome, which includes conditioned media (CM) and soluble bioactive molecules, as well as extracellular vesicles extracted from CM. Hypoxia can play a role in immunomodulation and angiogenesis by altering the protein or nucleic acid components in the secretory group, which enhances the therapeutic potential of DSCs. This review summarizes the biological characteristics of DSCs, the influence of hypoxia on DSCs, the impact of hypoxia on the secretory group of DSCs, and the latest progress on the use of DSCs secretory group in tissue regeneration based on hypoxia pretreatment. We highlighted the multifunctional biological effect of hypoxia culture on tissue regeneration and provided a summary of the current mechanism of hypoxia in the pretreatment of DSCs.
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Affiliation(s)
- Yi Liu
- Department of Orthodontics, School and Hospital of Stomatology, Shenyang Clinical Medical Research Center of Orthodontic Disease, China Medical University, Shenyang, China
| | - Ling Ren
- Department of Orthodontics, School and Hospital of Stomatology, Shenyang Clinical Medical Research Center of Orthodontic Disease, China Medical University, Shenyang, China
| | - Mengyao Li
- Department of Orthodontics, School and Hospital of Stomatology, Shenyang Clinical Medical Research Center of Orthodontic Disease, China Medical University, Shenyang, China
| | - Bowen Zheng
- Department of Orthodontics, School and Hospital of Stomatology, Shenyang Clinical Medical Research Center of Orthodontic Disease, China Medical University, Shenyang, China
| | - Yi Liu
- Department of Orthodontics, School and Hospital of Stomatology, Shenyang Clinical Medical Research Center of Orthodontic Disease, China Medical University, Shenyang, China
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Ma M. Role of Hypoxia in Mesenchymal Stem Cells from Dental Pulp: Influence, Mechanism and Application. Cell Biochem Biophys 2024; 82:535-547. [PMID: 38713403 PMCID: PMC11344735 DOI: 10.1007/s12013-024-01274-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/08/2024] [Indexed: 05/08/2024]
Abstract
Mesenchymal stem cells (MSCs) from dental pulp (DP-MSCs), which include dental pulp stem cells (DPSCs) isolated from permanent teeth and stem cells from human exfoliated deciduous teeth (SHED), have emerged as highly promising cell sources for tissue regeneration, due to their high proliferative rate, multi-lineage differentiation capability and non-invasive accessibility. DP-MSCs also exert extensive paracrine effects through the release of extracellular vesicles (EVs) and multiple trophic factors. To be noted, the microenvironment, commonly referred to as the stem cell niche, plays a crucial role in shaping the functionality and therapeutic effects of DP-MSCs, within which hypoxia has garnered considerable attention. Extensive research has demonstrated that hypoxic conditions profoundly impact DP-MSCs. Specifically, hypoxia promotes DP-MSC proliferation, survival, stemness, migration, and pro-angiogenic potential while modulating their multi-lineage differentiation capacity. Furthermore, hypoxia stimulates the paracrine activities of DP-MSCs, leading to an increased production of EVs and soluble factors. Considering these findings, hypoxia preconditioning has emerged as a promising approach to enhance the therapeutic potential of DP-MSCs. In this comprehensive review, we provide a systematic overview of the influence of hypoxia on DP-MSCs, shedding light on the underlying mechanisms involved. Moreover, we also discuss the potential applications of hypoxia-preconditioned DP-MSCs or their secretome in tissue regeneration. Additionally, we delve into the methodologies employed to simulate hypoxic environments. This review aims to promote a comprehensive and systematic understanding of the hypoxia-induced effects on DP-MSCs and facilitate the refinement of regenerative therapeutic strategies based on DP-MSCs.
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Affiliation(s)
- Muyuan Ma
- School of Medicine, South China University of Technology, Guangzhou, China.
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Bai X, Cao R, Wu D, Zhang H, Yang F, Wang L. Dental Pulp Stem Cells for Bone Tissue Engineering: A Literature Review. Stem Cells Int 2023; 2023:7357179. [PMID: 37868704 PMCID: PMC10586346 DOI: 10.1155/2023/7357179] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 06/03/2023] [Accepted: 09/19/2023] [Indexed: 10/24/2023] Open
Abstract
Bone tissue engineering (BTE) is a promising approach for repairing and regenerating damaged bone tissue, using stem cells and scaffold structures. Among various stem cell sources, dental pulp stem cells (DPSCs) have emerged as a potential candidate due to their multipotential capabilities, ability to undergo osteogenic differentiation, low immunogenicity, and ease of isolation. This article reviews the biological characteristics of DPSCs, their potential for BTE, and the underlying transcription factors and signaling pathways involved in osteogenic differentiation; it also highlights the application of DPSCs in inducing scaffold tissues for bone regeneration and summarizes animal and clinical studies conducted in this field. This review demonstrates the potential of DPSC-based BTE for effective bone repair and regeneration, with implications for clinical translation.
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Affiliation(s)
- Xiaolei Bai
- Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Ruijue Cao
- Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Danni Wu
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Huicong Zhang
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Fan Yang
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Linhong Wang
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
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Xu N, Li LS, Li H, Zhang LH, Zhang N, Wang PJ, Cheng YX, Xiang JY, Linghu EQ, Chai NL. SGK3 overexpression correlates with a poor prognosis in endoscopically resected superficial esophageal squamous cell neoplasia: A long-term study. World J Gastroenterol 2023; 29:3658-3667. [PMID: 37398883 PMCID: PMC10311610 DOI: 10.3748/wjg.v29.i23.3658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 03/20/2023] [Accepted: 05/23/2023] [Indexed: 06/16/2023] Open
Abstract
BACKGROUND The expression status of serum and glucocorticoid-induced protein kinase 3 (SGK3) in superficial esophageal squamous cell neoplasia (ESCN) remains unknown. AIM To evaluate the SGK3 overexpression rate in ESCN and its influence on the prognosis and outcomes of patients with endoscopic resection. METHODS A total of 92 patients who had undergone endoscopic resection for ESCN with more than 8 years of follow-up were enrolled. Immunohistochemistry was used to evaluate SGK3 expression. RESULTS SGK3 was overexpressed in 55 (59.8%) patients with ESCN. SGK3 overexpression showed a significant correlation with death (P = 0.031). Overall survival and disease-free survival rates were higher in the normal SGK3 expression group than in the SGK3 overexpression group (P = 0.013 and P = 0.004, respectively). Cox regression analysis models demonstrated that SGK3 overexpression was an independent predictor of poor prognosis in ESCN patients (hazard ratio 4.729; 95% confidence interval: 1.042-21.458). CONCLUSION SGK3 overexpression was detected in the majority of patients with endoscopically resected ESCN and was significantly associated with shortened survival. Thus, it might be a new prognostic factor for ESCN.
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Affiliation(s)
- Ning Xu
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing 100853, China
| | - Long-Song Li
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing 100853, China
| | - Hui Li
- Department of Gastroenterology, Air Force Medical Center, Beijing 100142, China
| | - Li-Hua Zhang
- Department of Pathology, The Fourth Medical Center of PLA General Hospital, Beijing 100142, China
| | - Nan Zhang
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing 100853, China
| | - Peng-Ju Wang
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing 100853, China
| | - Ya-Xuan Cheng
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing 100853, China
| | - Jing-Yuan Xiang
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing 100853, China
| | - En-Qiang Linghu
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing 100853, China
| | - Ning-Li Chai
- Senior Department of Gastroenterology, The First Medical Center of PLA General Hospital, Beijing 100853, China
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Kim Y, Park HJ, Kim MK, Kim YI, Kim HJ, Bae SK, Nör JE, Bae MK. Naringenin stimulates osteogenic/odontogenic differentiation and migration of human dental pulp stem cells. J Dent Sci 2023; 18:577-585. [PMID: 37021242 PMCID: PMC10068380 DOI: 10.1016/j.jds.2022.08.029] [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: 08/08/2022] [Revised: 08/25/2022] [Indexed: 11/21/2022] Open
Abstract
Background/purpose Naringenin, a naturally occurring flavanone in citrus fruits, regulates bone formation by bone marrow-derived mesenchymal stem cells. The purpose of this study was to characterize the effects of naringenin on some biological behaviors of human dental pulp stem cells (HDPSCs). Materials and methods HDPSCs were cultured in osteogenic differentiation medium and osteo/odontogenic differentiation and mineralization were analyzed by alkaline phosphatase (ALP) staining and Alizarin Red S (ARS) staining. The migration of HDPSCs was evaluated by transwell chemotactic migration assays and scratch wound healing migration assay. Using tooth slice/scaffold model, we assessed the in vivo odontogenic differentiation potential of HDPSCs. Results We have demonstrated that naringenin increases the osteogenic/odontogenic differentiation of HDPSCs through regulation of osteogenic-related proteins and the migratory ability of HDPSCs through stromal cell derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) axis. Moreover, naringenin promotes the expression of dentin matrix acidic phosphoprotein-1 (DMP-1) and dentin sialophosphoprotein (DSPP) in HDPSCs seeded on tooth slice/scaffolds that are subcutaneously implanted into immunodeficient mice. Conclusion Our present study suggests that naringenin promotes migration and osteogenic/odontogenic differentiation of HDPSCs and may serve as a promising candidate in dental tissue engineering and bone regeneration.
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Affiliation(s)
- Yeon Kim
- Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan, South Korea
- Periodontal Disease Signaling Network Research Center (MRC), Pusan National University, Yangsan, South Korea
- Dental and Life Science Institute, Pusan National University, Yangsan, South Korea
| | - Hyun-Joo Park
- Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan, South Korea
- Periodontal Disease Signaling Network Research Center (MRC), Pusan National University, Yangsan, South Korea
- Dental and Life Science Institute, Pusan National University, Yangsan, South Korea
| | - Mi-Kyoung Kim
- Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan, South Korea
- Periodontal Disease Signaling Network Research Center (MRC), Pusan National University, Yangsan, South Korea
| | - Yong-Il Kim
- Department of Orthodontics, School of Dentistry, Pusan National University, Yangsan, South Korea
| | - Hyung Joon Kim
- Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan, South Korea
- Periodontal Disease Signaling Network Research Center (MRC), Pusan National University, Yangsan, South Korea
- Dental and Life Science Institute, Pusan National University, Yangsan, South Korea
| | - Soo-Kyung Bae
- Periodontal Disease Signaling Network Research Center (MRC), Pusan National University, Yangsan, South Korea
- Dental and Life Science Institute, Pusan National University, Yangsan, South Korea
- Department of Dental Pharmacology, School of Dentistry, Pusan National University, Yangsan, South Korea
| | - Jacques E. Nör
- Department of Cariology, Restorative Sciences, Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA
| | - Moon-Kyoung Bae
- Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan, South Korea
- Periodontal Disease Signaling Network Research Center (MRC), Pusan National University, Yangsan, South Korea
- Dental and Life Science Institute, Pusan National University, Yangsan, South Korea
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Okić-Đorđević I, Obradović H, Kukolj T, Petrović A, Mojsilović S, Bugarski D, Jauković A. Dental mesenchymal stromal/stem cells in different microenvironments— implications in regenerative therapy. World J Stem Cells 2021; 13:1863-1880. [PMID: 35069987 PMCID: PMC8727232 DOI: 10.4252/wjsc.v13.i12.1863] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/15/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Current research data reveal microenvironment as a significant modifier of physical functions, pathologic changes, as well as the therapeutic effects of stem cells. When comparing regeneration potential of various stem cell types used for cytotherapy and tissue engineering, mesenchymal stem cells (MSCs) are currently the most attractive cell source for bone and tooth regeneration due to their differentiation and immunomodulatory potential and lack of ethical issues associated with their use. The microenvironment of donors and recipients selected in cytotherapy plays a crucial role in regenerative potential of transplanted MSCs, indicating interactions of cells with their microenvironment indispensable in MSC-mediated bone and dental regeneration. Since a variety of MSC populations have been procured from different parts of the tooth and tooth-supporting tissues, MSCs of dental origin and their achievements in capacity to reconstitute various dental tissues have gained attention of many research groups over the years. This review discusses recent advances in comparative analyses of dental MSC regeneration potential with regards to their tissue origin and specific microenvironmental conditions, giving additional insight into the current clinical application of these cells.
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Affiliation(s)
- Ivana Okić-Đorđević
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Hristina Obradović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Tamara Kukolj
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Anđelija Petrović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Slavko Mojsilović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Diana Bugarski
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Aleksandra Jauković
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
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Wang D, Jiang S, Zhang F, Ma S, Heng BC, Wang Y, Zhu J, Xu M, He Y, Wei Y, Zhang X, Xia B, Deng X. Cell Membrane Vesicles with Enriched CXCR4 Display Enhances Their Targeted Delivery as Drug Carriers to Inflammatory Sites. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2021; 8:e2101562. [PMID: 34687286 PMCID: PMC8655180 DOI: 10.1002/advs.202101562] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 08/02/2021] [Indexed: 06/13/2023]
Abstract
Cell membrane vesicles (CMVs) are composed of natural cell membranes which makes them effective drug delivery systems with low immunogenicity and prolonged circulation time. However, targeting delivery of CMVs in vivo for clinical applications is still a major challenge. In this study, CXCR4 recombinant lentivirus is transfected into MC-3T3 cells and membrane CXCR4-enriched MC-3T3 cells are obtained. CMVs with enriched membrane CXCR4 display (CXCR4-CMVs) are obtained from the transfected MC-3T3 cells. Curcumin, an effective natural anti-inflammatory compound, is encapsulated into CXCR4-CMVs through physical entrapment (CXCR4/Cur-CMVs), with the membrane integrity of CXCR4/Cur-CMVs being well-preserved. CXCR4/Cur-CMVs induce enhanced M2 macrophage polarization, exhibit anti-inflammatory effects, and significantly improve homing via the CXCR4/CXCL12 axis in vitro. Utilizing ulcerative colitis and apical periodontitis as inflammatory disease models, it is found that CXCR4/Cur-CMVs are obviously aggregated within inflammatory areas after intravenous administration, which results in significant amelioration of ulcerative colitis and apical periodontitis. Therefore, this research may provide a feasible and innovative approach for fabricating an inflammatory site-targeting delivery system, by engineering CMVs to increase membrane-presenting CXCR4 receptor.
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Affiliation(s)
- Dandan Wang
- Department of Pediatric Dentistry, School and Hospital of Stomatology, Peking University, Beijing, 100081, P. R. China
| | - Shengjie Jiang
- Beijing Laboratory of Biomedical Materials, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Fengyi Zhang
- Beijing Laboratory of Biomedical Materials, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Siqin Ma
- Beijing Laboratory of Biomedical Materials, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Boon Chin Heng
- Beijing Laboratory of Biomedical Materials, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Yuanyuan Wang
- Department of Pediatric Dentistry, School and Hospital of Stomatology, Peking University, Beijing, 100081, P. R. China
| | - Junxia Zhu
- Department of Pediatric Dentistry, School and Hospital of Stomatology, Peking University, Beijing, 100081, P. R. China
| | - Mingming Xu
- Beijing Laboratory of Biomedical Materials, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Ying He
- Beijing Laboratory of Biomedical Materials, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Yan Wei
- Beijing Laboratory of Biomedical Materials, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Xuehui Zhang
- Department of Dental Materials & Dental Medical Devices Testing Center, National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Bin Xia
- Department of Pediatric Dentistry, School and Hospital of Stomatology, Peking University, Beijing, 100081, P. R. China
| | - Xuliang Deng
- Beijing Laboratory of Biomedical Materials, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
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11
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Fu J, Wang Y, Jiang Y, Du J, Xu J, Liu Y. Systemic therapy of MSCs in bone regeneration: a systematic review and meta-analysis. Stem Cell Res Ther 2021; 12:377. [PMID: 34215342 PMCID: PMC8254211 DOI: 10.1186/s13287-021-02456-w] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Accepted: 06/12/2021] [Indexed: 12/30/2022] Open
Abstract
Objectives Over the past decades, many studies focused on mesenchymal stem cells (MSCs) therapy for bone regeneration. Due to the efficiency of topical application has been widely dicussed and systemic application was also a feasible way for new bone formation, the aim of this study was to systematically review systemic therapy of MSCs for bone regeneration in pre-clinical studies. Methods The article search was conducted in PubMed and Embase databases. Original research articles that assessed potential effect of systemic application of MSCs for bone regeneration in vivo were selected and evaluated in this review, according to eligibility criteria. The efficacy of MSC systemic treatment was analyzed by random effects meta-analysis, and the outcomes were expressed in standard mean difference (SMD) and its 95% confidence interval. Subgroup analyses were conducted on animal species and gender, MSCs types, frequency and time of injection, and bone diseases. Results Twenty-three articles were selected in this review, of which 21 were included in meta-analysis. The results showed that systemic therapy increased bone mineral density (SMD 3.02 [1.84, 4.20]), bone volume to tissue volume ratio (2.10 [1.16, 3.03]), and the percentage of new bone area (7.03 [2.10, 11.96]). Bone loss caused by systemic disease tended to produce a better response to systemic treatment (p=0.05 in BMD, p=0.03 in BV/TV). Conclusion This study concluded that systemic therapy of MSCs promotes bone regeneration in preclinical experiments. These results provided important information for the systemic application of MSCs as a potential application of bone formation in further animal experiments. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-021-02456-w.
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Affiliation(s)
- Jingfei Fu
- 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, Tian Tan Xi Li No.4, Beijing, 100050, People's Republic of China
| | - Yanxue Wang
- 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, Tian Tan Xi Li No.4, Beijing, 100050, People's Republic of China
| | - Yiyang Jiang
- 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, Tian Tan Xi Li No.4, Beijing, 100050, People's Republic of China
| | - Juan Du
- 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, Tian Tan Xi Li No.4, Beijing, 100050, People's Republic of China
| | - Junji Xu
- 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, Tian Tan Xi Li No.4, Beijing, 100050, People's Republic of China.
| | - Yi 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, Tian Tan Xi Li No.4, Beijing, 100050, People's Republic of China.
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12
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Hu X, Wang L, He Y, Wei M, Yan H, Zhu H. Chlorogenic Acid Promotes Osteogenic Differentiation of Human Dental Pulp Stem Cells Through Wnt Signaling. Stem Cells Dev 2021; 30:641-650. [PMID: 33789447 DOI: 10.1089/scd.2020.0193] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Periodontal disease (PD) is one of the main causes of periodontal bone resorption and tooth loss in adults. How to repair the alveolar bone effectively has always been a challenge. This study was designed to clarify the effects and the underlying molecular mechanisms of chlorogenic acid (CGA) on osteogenic differentiation of human dental pulp stem cells (hDPSCs). In this study, we used CGA to treat hDPSCs. The osteogenic experiment showed that CGA can promote hDPSCs osteogenic differentiation. RNA-Seq and quantitative real-time polymerase chain reaction showed that CGA treatment enhanced the expression of the osteogenesis genes for frizzled-related protein (FRZB) and pyruvate dehydrogenase kinase 4 (PDK4) and inhibit the expression of the osteoclastogenesis genes such as those for asporin (ASPN) and cytokine-like 1 (CYTL1). Western blot analysis showed that besides FRZB, CGA treatment also caused reduction of both active and total β-catenin, while increased the total calcium/calmodulin-dependent kinase II (CamKII), the phosphorylated CamKII (pCamKII) and the phosphorylated cAMP-response element-binding protein (pCREB). Likely, the increased osteogenesis was associated with reduced canonical Wnt/β-catenin signaling but increased noncanonical Wnt/Ca2+ signaling. The results suggested that CGA can promote the osteogenic differentiation of hDPSCs by regulating Wnt signaling. These findings will serve as a foundation for further studies on how to repair defective alveolar bone for the patients with PD.
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Affiliation(s)
- Xiaoping Hu
- The Key Laboratory of Oral Biomedicine, Affiliated Stomatological Hospital of Nanchang University, Nanchang, P.R. China
| | - Li Wang
- Affiliated Stomatological Hospital of Nanchang University, Jiangxi Medical College of Nanchang University, Nanchang, P.R. China
| | - Yuanqiao He
- Department of Laboratory Animal Science, Nanchang University, Nanchang, P.R. China.,Jiangxi Province Key Laboratory of Laboratory Animal Nanchang Royo Biotech Co., Ltd., Nanchang, P.R. China
| | - Minli Wei
- Key Laboratory of Reproductive Physiology and Pathology in Jiangxi Province, Jiangxi Medical College of Nanchang University, Nanchang, P.R. China
| | - Huilin Yan
- Key Laboratory of Reproductive Physiology and Pathology in Jiangxi Province, Jiangxi Medical College of Nanchang University, Nanchang, P.R. China
| | - Hongshui Zhu
- The Key Laboratory of Oral Biomedicine, Affiliated Stomatological Hospital of Nanchang University, Nanchang, P.R. China
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13
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Colombo JS, Jia S, D'Souza RN. Modeling Hypoxia Induced Factors to Treat Pulpal Inflammation and Drive Regeneration. J Endod 2020; 46:S19-S25. [DOI: 10.1016/j.joen.2020.06.039] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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14
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Novais A, Lesieur J, Sadoine J, Slimani L, Baroukh B, Saubaméa B, Schmitt A, Vital S, Poliard A, Hélary C, Rochefort GY, Chaussain C, Gorin C. Priming Dental Pulp Stem Cells from Human Exfoliated Deciduous Teeth with Fibroblast Growth Factor-2 Enhances Mineralization Within Tissue-Engineered Constructs Implanted in Craniofacial Bone Defects. Stem Cells Transl Med 2019; 8:844-857. [PMID: 31016898 PMCID: PMC6646701 DOI: 10.1002/sctm.18-0182] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 12/03/2018] [Indexed: 12/17/2022] Open
Abstract
The craniofacial area is prone to trauma or pathologies often resulting in large bone damages. One potential treatment option is the grafting of a tissue-engineered construct seeded with adult mesenchymal stem cells (MSCs). The dental pulp appears as a relevant source of MSCs, as dental pulp stem cells display strong osteogenic properties and are efficient at bone formation and repair. Fibroblast growth factor-2 (FGF-2) and/or hypoxia primings were shown to boost the angiogenesis potential of dental pulp stem cells from human exfoliated deciduous teeth (SHED). Based on these findings, we hypothesized here that these primings would also improve bone formation in the context of craniofacial bone repair. We found that both hypoxic and FGF-2 primings enhanced SHED proliferation and osteogenic differentiation into plastically compressed collagen hydrogels, with a much stronger effect observed with the FGF-2 priming. After implantation in immunodeficient mice, the tissue-engineered constructs seeded with FGF-2 primed SHED mediated faster intramembranous bone formation into critical size calvarial defects than the other groups (no priming and hypoxia priming). The results of this study highlight the interest of FGF-2 priming in tissue engineering for craniofacial bone repair. Stem Cells Translational Medicine 2019;8:844&857.
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Affiliation(s)
- Anita Novais
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
- AP‐HP Département d'OdontologieHôpitaux Universitaires PNVS, Charles Foix et Henri MondorIle de FranceFrance
| | - Julie Lesieur
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
| | - Jérémy Sadoine
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
| | - Lotfi Slimani
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
| | - Brigitte Baroukh
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
| | - Bruno Saubaméa
- Cellular and Molecular Imaging FacilityInserm US25, CNRS UMS 3612, Faculté de Pharmacie de Paris, Université Paris Descartes Sorbonne Paris CitéParisFrance
| | - Alain Schmitt
- Cochin Institute, Transmission Electron Microscopy Platform, INSERM U1016, CNRS UMR8104Université Paris Descartes Sorbonne Paris CitéParisFrance
| | - Sibylle Vital
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
- AP‐HP Département d'OdontologieHôpitaux Universitaires PNVS, Charles Foix et Henri MondorIle de FranceFrance
| | - Anne Poliard
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
| | - Christophe Hélary
- Laboratoire de Chimie de la Matière Condensée de ParisSorbonne Universités, CNRS, Collège de FranceParisFrance
| | - Gaël Y. Rochefort
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
| | - Catherine Chaussain
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
- AP‐HP Département d'OdontologieHôpitaux Universitaires PNVS, Charles Foix et Henri MondorIle de FranceFrance
| | - Caroline Gorin
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
- AP‐HP Département d'OdontologieHôpitaux Universitaires PNVS, Charles Foix et Henri MondorIle de FranceFrance
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15
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Collignon AM, Castillo-Dali G, Gomez E, Guilbert T, Lesieur J, Nicoletti A, Acuna-Mendoza S, Letourneur D, Chaussain C, Rochefort GY, Poliard A. Mouse Wnt1-CRE
-Rosa
Tomato
Dental Pulp Stem Cells Directly Contribute to the Calvarial Bone Regeneration Process. Stem Cells 2019; 37:701-711. [DOI: 10.1002/stem.2973] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Revised: 12/14/2018] [Accepted: 12/19/2018] [Indexed: 01/08/2023]
Affiliation(s)
- Anne-Margaux Collignon
- EA 2496 Orofacial Pathologies, Imagery, and Biotherapies, Dental School Faculty; University Paris Descartes, and Life Imaging Platform (PIV); Montrouge France
- University Hospitals, AP-HP; Paris France
| | - Gabriel Castillo-Dali
- EA 2496 Orofacial Pathologies, Imagery, and Biotherapies, Dental School Faculty; University Paris Descartes, and Life Imaging Platform (PIV); Montrouge France
| | - Eduardo Gomez
- EA 2496 Orofacial Pathologies, Imagery, and Biotherapies, Dental School Faculty; University Paris Descartes, and Life Imaging Platform (PIV); Montrouge France
| | - Thomas Guilbert
- Plateforme IMAG'IC, Institut Cochin, Inserm U1016-CNRS UMR8104; University Paris Descartes; Paris France
| | - Julie Lesieur
- EA 2496 Orofacial Pathologies, Imagery, and Biotherapies, Dental School Faculty; University Paris Descartes, and Life Imaging Platform (PIV); Montrouge France
| | - Antonino Nicoletti
- INSERM U1148, Laboratory of Vascular Translational Science; University Paris Diderot, University Paris 13, Bichat Hospital, and Département Hospitalo-Universitaire (DHU) FIRE; Paris France
| | - Soledad Acuna-Mendoza
- EA 2496 Orofacial Pathologies, Imagery, and Biotherapies, Dental School Faculty; University Paris Descartes, and Life Imaging Platform (PIV); Montrouge France
| | - Didier Letourneur
- INSERM U1148, Laboratory of Vascular Translational Science; University Paris Diderot, University Paris 13, Bichat Hospital, and Département Hospitalo-Universitaire (DHU) FIRE; Paris France
| | - Catherine Chaussain
- EA 2496 Orofacial Pathologies, Imagery, and Biotherapies, Dental School Faculty; University Paris Descartes, and Life Imaging Platform (PIV); Montrouge France
- University Hospitals, AP-HP; Paris France
| | - Gael Y. Rochefort
- EA 2496 Orofacial Pathologies, Imagery, and Biotherapies, Dental School Faculty; University Paris Descartes, and Life Imaging Platform (PIV); Montrouge France
| | - Anne Poliard
- EA 2496 Orofacial Pathologies, Imagery, and Biotherapies, Dental School Faculty; University Paris Descartes, and Life Imaging Platform (PIV); Montrouge France
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16
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Dou L, Yan Q, Liang P, Zhou P, Zhang Y, Ji P. iTRAQ-Based Proteomic Analysis Exploring the Influence of Hypoxia on the Proteome of Dental Pulp Stem Cells under 3D Culture. Proteomics 2018; 18. [PMID: 29327447 DOI: 10.1002/pmic.201700215] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Revised: 08/21/2017] [Indexed: 12/14/2022]
Abstract
Hypoxic preconditioning is commonly applied to enhance mesenchymal stem cells (MSCs) therapeutic effect before transplantation. Elucidating the effect of hypoxic preconditioning would be beneficial for improved application. However, the influence of hypoxia on dental tissue derived MSCs cultured in 3D was unknown. Thus, the present study is to investigate gene expression and proteome of dental pulp stem cells (DPSCs) after hypoxic preconditioning. DPSCs were isolated, cultured in a 3D system under the normoxic and hypoxic conditions. The gene expression was examined with reverse transcription polymerase chain reaction, and the proteome was analyzed using iTRAQ-based mass spectrometry. The expressions of HIF-1α, VEGFA, KDR at mRNA level was upregulated while BMP-2 was downregulated. Two thousand one hundred and fifteen proteins were identified and 57 proteins exhibited significant differences after hypoxic preconditioning (30 up-regulated, 27 down-regulated). Bioinformatic analysis revealed the majority of up-regulated proteins are involved in cellular process, angiogenesis, protein binding and transport, regulation of response to stimulus, metabolic processes, and immune response. Increased IL-6 and decreased TGF-1β protein expression under hypoxic condition were verified by ELISA. Hypoxic preconditioning partly affected the gene and protein expression in DPSCs under 3D culture and may enhance the efficacy of MSCs transplantation.
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Affiliation(s)
- Lei Dou
- Stomatological hospital of Chongqing medical university, Chongqing, P. R. China.,Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing, P. R. China.,Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, P. R. China
| | - Qifang Yan
- Stomatological hospital of Chongqing medical university, Chongqing, P. R. China.,Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing, P. R. China.,Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, P. R. China
| | - Panpan Liang
- Stomatological hospital of Chongqing medical university, Chongqing, P. R. China.,Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing, P. R. China.,Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, P. R. China
| | - Pengfei Zhou
- Stomatological hospital of Chongqing medical university, Chongqing, P. R. China.,Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing, P. R. China.,Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, P. R. China
| | - Yan Zhang
- Stomatological hospital of Chongqing medical university, Chongqing, P. R. China.,Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing, P. R. China.,Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, P. R. China
| | - Ping Ji
- Stomatological hospital of Chongqing medical university, Chongqing, P. R. China.,Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing, P. R. China.,Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, P. R. China
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17
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Yan Y, Qi S, Gong SQ, Shang G, Zhao Y. Effect of CRABP2 on the proliferation and odontoblastic differentiation of hDPSCs. Braz Oral Res 2017; 31:e112. [PMID: 29267673 DOI: 10.1590/1807-3107bor-2017.vol31.0112] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 11/23/2017] [Indexed: 11/21/2022] Open
Abstract
Cellular retinoic acid-binding protein 2 (CRABP2) has been detected in several organs during embryonic development. Recent studies have demonstrated that CRABP2 plays important roles in the retinoic acid, β-catenin and Notch signaling pathways, as well as in the interaction between epithelial and mesenchymal cells, which are important for human dental pulp stem cells (hDPSCs) and tooth development. In the present study, the expression of CRABP2 during mouse molar development and the role of CRABP2 in hDPSC odontoblastic differentiation were evaluated. CRABP2 was gradually decreased during the development of the first maxillary molar, which exhibited the same trend as the expression of CRABP2 during the odontoblastic induction of hDPSCs. CRABP2 knockdown inhibited the proliferative ability of hDPSCs, while it enhanced odontoblastic differentiation via promoting mineralization nodule formation and upregulating the activity of alkaline phosphatase and the expression of mineralization-related genes. The present study uncovered a novel function of CRABP2 in hDPSCs. Our data suggest that CRABP2 may act as a regulator during the proliferation and differentiation of hDPSCs.
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Affiliation(s)
- Yanhong Yan
- Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Department of Pediatric Dentistry, Shanghai, China
| | - Shengcai Qi
- Shanghai Tenth People's Hospital of Tongji University, Department of Stomatology, Shanghai, China
| | - Shi-Qiang Gong
- Huazhong University of Science and Technology, Tongji Hospital, Center of Stomatology, Wuhan, China
| | - Guangwei Shang
- Shanghai Tenth People's Hospital of Tongji University, Department of Stomatology, Shanghai, China
| | - Yumei Zhao
- Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Department of Pediatric Dentistry, Shanghai, China
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