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Gao P, Kajiya M, Motoike S, Ikeya M, Yang J. Application of mesenchymal stem/stromal cells in periodontal regeneration: Opportunities and challenges. JAPANESE DENTAL SCIENCE REVIEW 2024; 60:95-108. [PMID: 38314143 PMCID: PMC10837070 DOI: 10.1016/j.jdsr.2024.01.001] [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: 08/08/2023] [Revised: 12/06/2023] [Accepted: 01/15/2024] [Indexed: 02/06/2024] Open
Abstract
Guided tissue regeneration (GTR) has been widely used in the periodontal treatment of intrabony and furcation defects for nearly four decades. The treatment outcomes have shown effectiveness in reducing pocket depth, improving attachment gain and bone filling in periodontal tissue. Although applying GTR could reconstruct the periodontal tissue, the surgical indications are relatively narrow, and some complications and race ethic problems bring new challenges. Therefore, it is challenging to achieve a consensus concerning the clinical benefits of GTR. With the appearance of stem cell-based regenerative medicine, mesenchymal stem/stromal cells (MSCs) have been considered a promising cell resource for periodontal regeneration. In this review, we highlight preclinical and clinical periodontal regeneration using MSCs derived from distinct origins, including non-odontogenic and odontogenic tissues and induced pluripotent stem cells, and discuss the transplantation procedures, therapeutic mechanisms, and concerns to evaluate the effectiveness of MSCs.
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Affiliation(s)
- Pan Gao
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of General Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Mikihito Kajiya
- Department of Periodontal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
| | - Souta Motoike
- Department of Periodontal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
| | - Makoto Ikeya
- Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan
| | - Jingmei Yang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
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Inchingolo AM, Inchingolo AD, Nardelli P, Latini G, Trilli I, Ferrante L, Malcangi G, Palermo A, Inchingolo F, Dipalma G. Stem Cells: Present Understanding and Prospects for Regenerative Dentistry. J Funct Biomater 2024; 15:308. [PMID: 39452606 PMCID: PMC11508604 DOI: 10.3390/jfb15100308] [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: 08/05/2024] [Revised: 10/02/2024] [Accepted: 10/11/2024] [Indexed: 10/26/2024] Open
Abstract
Regenerative medicine in dentistry focuses on repairing damaged oral tissues using advanced tools like stem cells, biomaterials, and tissue engineering (TE). Mesenchymal stem cells (MSCs) from dental sources, such as dental pulp and periodontal ligament, show significant potential for tissue regeneration due to their proliferative and differentiative abilities. This systematic review, following PRISMA guidelines, evaluated fifteen studies and identified effective strategies for improving dental, periodontal, and bone tissue regeneration through scaffolds, secretomes, and bioengineering methods. Key advancements include the use of dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) to boost cell viability and manage inflammation. Additionally, pharmacological agents like matrine and surface modifications on biomaterials improve stem cell adhesion and promote osteogenic differentiation. By integrating these approaches, regenerative medicine and TE can optimize dental therapies and enhance patient outcomes. This review highlights the potential and challenges in this field, providing a critical assessment of current research and future directions.
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Affiliation(s)
- Angelo Michele Inchingolo
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
| | - Alessio Danilo Inchingolo
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
| | - Paola Nardelli
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
| | - Giulia Latini
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
| | - Irma Trilli
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
| | - Laura Ferrante
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
| | - Giuseppina Malcangi
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
| | - Andrea Palermo
- College of Medicine and Dentistry, Birmingham B4 6BN, UK;
| | - Francesco Inchingolo
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
| | - Gianna Dipalma
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
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Moggio M, La Noce M, Tirino V, Papaccio G, Lepore M, Diano N. Sphingolipidomic profiling of human Dental Pulp Stem Cells undergoing osteogenic differentiation. Chem Phys Lipids 2024; 263:105420. [PMID: 39053614 DOI: 10.1016/j.chemphyslip.2024.105420] [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: 03/27/2024] [Revised: 07/18/2024] [Accepted: 07/22/2024] [Indexed: 07/27/2024]
Abstract
It is now recognized that sphingolipids are involved in the regulation and pathophysiology of several cellular processes such as proliferation, migration, and survival. Growing evidence also implicates them in regulating the behaviour of stem cells, the use of which is increasingly finding application in regenerative medicine. A shotgun lipidomic study was undertaken to determine whether sphingolipid biomarkers exist that can regulate the proliferation and osteogenic differentiation of human Dental Pulp Stem Cells (hDPSCs). Sphingolipids were extracted and identified by direct infusion into an electrospray mass spectrometer. By using cells cultured in osteogenic medium and in medium free of osteogenic stimuli, as a control, we analyzed and compared the SPLs profiles. Both cellular systems were treated at different times (72 hours, 7 days, and 14 days) to highlight any changes in the sphingolipidomic profiles in the subsequent phases of the differentiation process. Signals from sphingolipid species demonstrating clear differences were selected, their relative abundance was determined, and statistical differences were analyzed. Thus, our work suggests a connection between sphingolipid metabolism and hDPSC osteogenic differentiation and provides new biomarkers for improving hDPSC-based orthopaedic regenerative medicine.
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Affiliation(s)
- Martina Moggio
- Department of Experimental Medicine - University of Campania "L. Vanvitelli", Via S. M. di Costantinopoli, 16, Naples 80138, Italy
| | - Marcella La Noce
- Department of Experimental Medicine - University of Campania "L. Vanvitelli", Via S. M. di Costantinopoli, 16, Naples 80138, Italy
| | - Virginia Tirino
- Department of Experimental Medicine - University of Campania "L. Vanvitelli", Via S. M. di Costantinopoli, 16, Naples 80138, Italy
| | - Gianpaolo Papaccio
- Department of Experimental Medicine - University of Campania "L. Vanvitelli", Via S. M. di Costantinopoli, 16, Naples 80138, Italy
| | - Maria Lepore
- Department of Experimental Medicine - University of Campania "L. Vanvitelli", Via S. M. di Costantinopoli, 16, Naples 80138, Italy
| | - Nadia Diano
- Department of Experimental Medicine - University of Campania "L. Vanvitelli", Via S. M. di Costantinopoli, 16, Naples 80138, Italy.
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Yu X, Ge J, Xie H, Qian J, Xia W, Wang Q, Zhou X, Zhou Y. MiR-483-3p promotes dental pulp stem cells osteogenic differentiation via the MAPK signaling pathway by targeting ARRB2. In Vitro Cell Dev Biol Anim 2024; 60:879-887. [PMID: 38833209 DOI: 10.1007/s11626-024-00929-9] [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: 03/14/2024] [Accepted: 05/20/2024] [Indexed: 06/06/2024]
Abstract
Human dental pulp stem cells (DPSCs) have become an important component for bone tissue engineering and regenerative medicine due to their ability to differentiate into osteoblast precursors. Two miRNA chip datasets (GSE138180 and E-MTAB-3077) of DPSCs osteogenic differentiation were analyzed respectively to find the expression of miR-483-3p significantly increased in the differentiated groups. We further confirmed that miR-483-3p continued to overexpress during osteogenic differentiation of DPSCs, especially reaching its peak on the 7th day. Moreover, miR-483-3p could significantly promote the expression of osteogenic markers including RUNX2 and OSX, and activate MAPK signaling pathway by inducing phosphorylation of ERK, p38, and JNK. In addition, as a significant gene within the MAPK signaling pathway, ARRB2 was identified as the target gene of miR-483-3p by bioinformatic prediction and experimental verification. In conclusion, we identified miR-483-3p could promote osteogenic differentiation of DPSCs via the MAPK signaling pathway by targeting ARRB2.
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Affiliation(s)
- Xin Yu
- Department of Orthodontics and Periodontology, Affiliated Nantong Stomatological Hospital of Nantong University, 36 South Yuelong Road, Nantong, 226001, China
| | - Juan Ge
- Department of Immunology, School of Medicine, Nantong University, Nantong, China
| | - Huimin Xie
- Department of Orthodontics and Periodontology, Affiliated Nantong Stomatological Hospital of Nantong University, 36 South Yuelong Road, Nantong, 226001, China
| | - Jialu Qian
- Department of Clinical Laboratory, The First People's Hospital of Nantong, The Second Affiliated Hospital of Nantong University, Nantong, China
| | - Wenqian Xia
- Department of Orthodontics and Periodontology, Affiliated Nantong Stomatological Hospital of Nantong University, 36 South Yuelong Road, Nantong, 226001, China
| | - Qinghua Wang
- Laboratory Animal Center, Nantong University, Nantong, China
| | - Xiaorong Zhou
- Department of Immunology, School of Medicine, Nantong University, Nantong, China.
| | - Yan Zhou
- Department of Orthodontics and Periodontology, Affiliated Nantong Stomatological Hospital of Nantong University, 36 South Yuelong Road, Nantong, 226001, China.
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Zhou J, Sui M, Ji F, Shen S, Lin Y, Jin M, Tao J. Hsa_circ_0036872 has an important promotional effect in enhancing osteogenesis of dental pulp stem cells by regulating the miR-143-3p/IGF2 axis. Int Immunopharmacol 2024; 130:111744. [PMID: 38412676 DOI: 10.1016/j.intimp.2024.111744] [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: 01/05/2024] [Revised: 02/12/2024] [Accepted: 02/20/2024] [Indexed: 02/29/2024]
Abstract
BACKGROUND Circular RNAs (circRNAs), an extremely stable group of RNAs, possess a covalent closed-loop configuration. Numerous studies have highlighted the involvement of circRNAs in physiological processes and the development of various diseases. The present study aimed to investigate how circRNA regulates the osteogenic differentiation of human dental pulp stem cells (hDPSCs). METHODS We isolated hDPSCs from dental pulp and used next-generation sequencing analysis to determine the differentially-expressed circRNAs during osteogenic differentiation. Bioinformatics and dual-luciferase reporter assays identified the downstream targets. The role of circRNAs in osteogenic differentiation was further confirmed through the use of heterotopic bone models. RESULTS We found that hsa_circ_0036872 expression was increased during osteogenic differentiation of hDPSCs, and downregulation of hsa_circ_0036872 inhibited their osteogenic differentiation. Dual-luciferase reporter assays showed that both miR-143-3p and IGF2 were downstream targets of hsa_circ_0036872. Overexpression of IGF2 or inhibition of miR-143-3p restored the osteogenic differentiation ability of hDPSCs after silencing hsa_circ_0036872. Overexpression of IGF2 reversed the inhibitory effect of miR-143-3p on osteogenic differentiation. CONCLUSION Taken together, our results show that hsa_circ_0036872 exerts an important promotional effect in enhancing the osteogenesis of dental pulp stem cells by regulating the miR-143-3p/IGF2 axis. These data suggest a novel therapeutic strategy for osteoporosis treatment and periodontal tissue regeneration.
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Affiliation(s)
- Jiaxin Zhou
- Department of General Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Meizhi Sui
- Department of General Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China; Department of Stomatology, Kashgar Prefecture Second People's Hospital, Kashgar Xinjiang 844000, China
| | - Fang Ji
- Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, ; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Shihui Shen
- Department of General Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Yueting Lin
- Department of General Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Mingming Jin
- Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Road, Pudong New Area, Shanghai 201318, China.
| | - Jiang Tao
- Department of General Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China.
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Aljarmakani O, Assad M. Evaluation of the efficacy of using dental pulp graft in the healing of the alveolar bone after impacted canine extraction: a prospective cohort study. Ann Med Surg (Lond) 2024; 86:1283-1288. [PMID: 38463053 PMCID: PMC10923306 DOI: 10.1097/ms9.0000000000001729] [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: 11/02/2023] [Accepted: 01/08/2024] [Indexed: 03/12/2024] Open
Abstract
Summary The purpose of this study was to evaluate the radiographic density of the alveolar bone of the maxilla after extraction of the impacted canines and using the pulp tissue as an autogenous graft. Materials and methods This prospective cohort study recruited 14 patients (8 females and 6 males) between 2021 and 2023, with an average age of 35 years. All participants had palatally impacted maxillary canines. The impacted teeth were extracted surgically. The extracted teeth were then used for autogenous grafting. The pulp tissue was removed, cut into small pieces, and placed on an absorbable gelatin sponge before being inserted into the extraction socket. The wound was subsequently closed meticulously. After 4 months, the bone density was assessed radiographically using the Hounsfield Scale on cone beam computed tomography scans. Results After 4 months, the mean radiographic bone density value in the extraction area was (652.77 ± 56.13 HU), while the average density of the original bone was (659.7 ± 39.6 HU). Conclusions Within the limits of this study, dental pulp tissue can be used to restore bony defects of the alveolar bone in the maxilla. However, further research is needed to confirm these findings.
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Affiliation(s)
- Omar Aljarmakani
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Tishreen University, Lattakia, Syria
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Abdolahinia ED, Golestani S, Seif S, Afra N, Aflatoonian K, Jalalian A, Valizadeh N, Abdollahinia ED. A review of the therapeutic potential of dental stem cells as scaffold-free models for tissue engineering application. Tissue Cell 2024; 86:102281. [PMID: 38070384 DOI: 10.1016/j.tice.2023.102281] [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: 08/26/2023] [Revised: 11/19/2023] [Accepted: 11/22/2023] [Indexed: 01/21/2024]
Abstract
In the realm of regenerative medicine, tissue engineering has introduced innovative approaches to facilitate tissue regeneration. Specifically, in pulp tissue engineering, both scaffold-based and scaffold-free techniques have been applied. Relevant articles were meticulously chosen from PubMed, Scopus, and Google Scholar databases through a comprehensive search spanning from October 2022 to December 2022. Despite the inherent limitations of scaffolding, including inadequate mechanical strength for hard tissues, insufficient vents for vessel penetration, immunogenicity, and suboptimal reproducibility-especially with natural polymeric scaffolds-scaffold-free tissue engineering has garnered significant attention. This methodology employs three-dimensional (3D) cell aggregates such as spheroids and cell sheets with extracellular matrix, facilitating precise regeneration of target tissues. The choice of technique aside, stem cells play a pivotal role in tissue engineering, with dental stem cells emerging as particularly promising resources. Their pluripotent nature, non-invasive extraction process, and unique properties render them highly suitable for scaffold-free tissue engineering. This study delves into the latest advancements in leveraging dental stem cells and scaffold-free techniques for the regeneration of various tissues. This paper offers a comprehensive summary of recent developments in the utilization of dental stem cells and scaffold-free methods for tissue generation. It explores the potential of these approaches to advance tissue engineering and their effectiveness in therapies aimed at tissue regeneration.
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Affiliation(s)
- Elaheh Dalir Abdolahinia
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Oral Science and Translation Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.
| | - Shayan Golestani
- Department of Oral and Maxillofacial Surgery, Dental School, Islamic Azad University, Isfahan ( Khorasgan) Branch, Isfahan, Iran
| | - Sepideh Seif
- Faculty of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Narges Afra
- Faculty of Dentistry, Hormozgan University of Medical Sciences, Bandarabbas, Iran
| | - Khotan Aflatoonian
- Department of Restorative Dentistry, Dental School, Shahed University of Medical Sciences, Tehran, Iran
| | - Ali Jalalian
- Faculty of Dentistry, Hamedan University of Medical Sciences, Hamedan, Iran
| | - Nasrin Valizadeh
- Chemistry Department, Sciences Faculty, Azarbaijan Shahid Madani University, Tabriz, Iran
| | - Elham Dalir Abdollahinia
- Fellowship of Endocrinology, Endocrinology Department, Tabriz University of Medical Sciences, Iran.
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Daneshian Y, Lewallen EA, Badreldin AA, Dietz AB, Stein GS, Cool SM, Ryoo HM, Cho YD, van Wijnen AJ. Fundamentals and Translational Applications of Stem Cells and Biomaterials in Dental, Oral and Craniofacial Regenerative Medicine. Crit Rev Eukaryot Gene Expr 2024; 34:37-60. [PMID: 38912962 DOI: 10.1615/critreveukaryotgeneexpr.2024053036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/25/2024]
Abstract
Regenerative dental medicine continuously expands to improve treatments for prevalent clinical problems in dental and oral medicine. Stem cell based translational opportunities include regenerative therapies for tooth restoration, root canal therapy, and inflammatory processes (e.g., periodontitis). The potential of regenerative approaches relies on the biological properties of dental stem cells. These and other multipotent somatic mesenchymal stem cell (MSC) types can in principle be applied as either autologous or allogeneic sources in dental procedures. Dental stem cells have distinct developmental origins and biological markers that determine their translational utility. Dental regenerative medicine is supported by mechanistic knowledge of the molecular pathways that regulate dental stem cell growth and differentiation. Cell fate determination and lineage progression of dental stem cells is regulated by multiple cell signaling pathways (e.g., WNTs, BMPs) and epigenetic mechanisms, including DNA modifications, histone modifications, and non-coding RNAs (e.g., miRNAs and lncRNAs). This review also considers a broad range of novel approaches in which stem cells are applied in combination with biopolymers, ceramics, and composite materials, as well as small molecules (agonistic or anti-agonistic ligands) and natural compounds. Materials that mimic the microenvironment of the stem cell niche are also presented. Promising concepts in bone and dental tissue engineering continue to drive innovation in dental and non-dental restorative procedures.
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Affiliation(s)
- Yasaman Daneshian
- Department of Biochemistry, University of Vermont Larner College of Medicine, Burlington, VT, United States of America
| | - Eric A Lewallen
- Department of Biological Sciences, Hampton University, Hampton, VA, USA
| | - Amr A Badreldin
- Laboratory of Molecular Signaling, Division of Oral and Systemic Health Sciences, School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA
| | - Allan B Dietz
- Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Gary S Stein
- Department of Biochemistry, University of Vermont Larner College of Medicine, Burlington, VT 05405; University of Vermont Cancer Center, University of Vermont Larner College of Medicine, Burlington, VT 05405
| | - Simon M Cool
- School of Chemical Engineering, The University of Queensland, Brisbane, Queensland, Australia
| | - Hyun-Mo Ryoo
- School of Dentistry, Seoul National University, 28 Yeonkun-dong, Chongro-gu Seoul, 110-749, Republic of Korea
| | - Young Dan Cho
- Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital, 101 Daehak‑no, Jongno‑gu, Seoul 03080, Republic of Korea
| | - Andre J van Wijnen
- Department of Biochemistry, University of Vermont, Burlington, VT 05405, USA
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Washio A, Kérourédan O, Tabata Y, Kokabu S, Kitamura C. Effect of Bioactive Glasses and Basic Fibroblast Growth Factor on Dental Pulp Cells. J Funct Biomater 2023; 14:568. [PMID: 38132822 PMCID: PMC10744375 DOI: 10.3390/jfb14120568] [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: 10/17/2023] [Revised: 12/15/2023] [Accepted: 12/15/2023] [Indexed: 12/23/2023] Open
Abstract
Ideal regeneration of hard tissue and dental pulp has been reported with the use of a combination of bioactive glass and basic fibroblast growth factor (bFGF). However, no previous study has investigated the molecular mechanisms underlying the processes induced by this combination in dental pulp cells. This study aimed to examine the cellular phenotype and transcriptional changes induced by the combination of bioactive glass solution (BG) and bFGF in dental pulp cells using phase-contrast microscopy, a cell counting kit-8 assay, alkaline phosphatase staining, and RNA sequence analysis. bFGF induced elongation of the cell process and increased the number of cells. Whereas BG did not increase ALP activity, it induced extracellular matrix-related genes in the dental pulp. In addition, the combination of BG and bFGF induces gliogenesis-related genes in the nervous system. This is to say, bFGF increased the viability of dental pulp cells, bioactive glass induced odontogenesis, and a dual stimulation with bioactive glass and bFGF induced the wound healing of the nerve system in the dental pulp. Taken together, bioactive glass and bFGF may be useful for the regeneration of the dentin-pulp complex.
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Affiliation(s)
- Ayako Washio
- Division of Endodontics and Restorative Dentistry, Department of Oral Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan;
| | - Olivia Kérourédan
- National Institute of Health and Medical Research (INSERM), U1026 BIOTIS, University of Bordeaux, 146 Rue Léo Saignat, 33076 Bordeaux, France;
| | - Yasuhiko Tabata
- Laboratory of Biomaterials, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan;
| | - Shoichiro Kokabu
- Division of Molecular Signaling and Biochemistry, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan;
| | - Chiaki Kitamura
- Division of Endodontics and Restorative Dentistry, Department of Oral Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan;
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Xing WB, Wu ST, Wang XX, Li FY, Wang RX, He JH, Fu J, He Y. Potential of dental pulp stem cells and their products in promoting peripheral nerve regeneration and their future applications. World J Stem Cells 2023; 15:960-978. [PMID: 37970238 PMCID: PMC10631371 DOI: 10.4252/wjsc.v15.i10.960] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 10/07/2023] [Accepted: 10/23/2023] [Indexed: 10/26/2023] Open
Abstract
Peripheral nerve injury (PNI) seriously affects people's quality of life. Stem cell therapy is considered a promising new option for the clinical treatment of PNI. Dental stem cells, particularly dental pulp stem cells (DPSCs), are adult pluripotent stem cells derived from the neuroectoderm. DPSCs have significant potential in the field of neural tissue engineering due to their numerous advantages, such as easy isolation, multidifferentiation potential, low immunogenicity, and low transplant rejection rate. DPSCs are extensively used in tissue engineering and regenerative medicine, including for the treatment of sciatic nerve injury, facial nerve injury, spinal cord injury, and other neurodegenerative diseases. This article reviews research related to DPSCs and their advantages in treating PNI, aiming to summarize the therapeutic potential of DPSCs for PNI and the underlying mechanisms and providing valuable guidance and a foundation for future research.
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Affiliation(s)
- Wen-Bo Xing
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Shu-Ting Wu
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Xin-Xin Wang
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Fen-Yao Li
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Ruo-Xuan Wang
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Ji-Hui He
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Jiao Fu
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Yan He
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- Department of Stomatology, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, Hubei Province, China.
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11
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Sonmez Kaplan S, Sazak Ovecoglu H, Genc D, Akkoc T. TNF-α, IL-1B and IL-6 affect the differentiation ability of dental pulp stem cells. BMC Oral Health 2023; 23:555. [PMID: 37568110 PMCID: PMC10422753 DOI: 10.1186/s12903-023-03288-1] [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: 01/26/2023] [Accepted: 08/05/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND This in vitro study examined the effect of the inflammatory cytokines (tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6) on osteogenic, chondrogenic, and adipogenic differentiation of dental pulp stem cells (DPSCs) which have significant relevance in future regenerative therapies. METHODS DPSCs were isolated from the impacted third molar dental pulp and determined with flow cytometry analysis. DPSCs were divided into into 5 main groups with 3 subdivisions for each group making a total of 15 groups. Experimental groups were stimulated with TNF-α, IL-1β, IL-6, and a combination of all three to undergo osteogenic, chondrogenic, and adipogenic differentiation protocols. Next, the differentiation of each group was examined with different staining procedures under a light microscope. Histological analysis of osteogenic, chondrogenic, and adipogenic differentiated pellets was assessed using a modified Bern score. Statistical significance determined using one-way analysis of variance, and correlations were assessed using Pearson's test (two-tailed). RESULTS Stimulation with inflammatory cytokines significantly inhibited the osteogenic, chondrogenic and adipogenic differentiation of DPSCs in terms of matrix and cell formation resulting in weak staining than the unstimulated groups with inflammatory cytokines. On contrary, the unstimulated groups of MSCs have shown to be highly proliferative ability in terms of osteogenic, chondrogenic, and adipogenic differentiation. CONCLUSIONS DPSCs have high osteogenic, chondrogenic, and adipogenic differentiation capabilities. Pretreatment with inflammatory cytokines decreases the differentiation ability in vitro, thus inhibiting tissue formation.
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Affiliation(s)
- Sema Sonmez Kaplan
- Department of Endodontics, Faculty of Dentistry, Biruni University, 10. Yıl Caddesi Protokol Yolu No: 45, 34010, Topkapı, Istanbul, Turkey.
| | - Hesna Sazak Ovecoglu
- Faculty of Dentistry Department of Endodontics, Marmara University, Istanbul, Turkey
| | - Deniz Genc
- Department of Pediatric Health & Diseases Faculty of Health Sciences, Muğla Sıtkı Koçman University, Mugla, Turkey
- Research Laboratories Center, Immunology and Stem Cell Laboratory, Muğla Sıtkı Koçman University, Mugla, Turkey
| | - Tunc Akkoc
- Immunology Department, Marmara University Medical Faculty, Istanbul, Turkey
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12
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Wang Z, Huang M, Zhang Y, Jiang X, Xu L. Comparison of Biological Properties and Clinical Application of Mesenchymal Stem Cells from the Mesoderm and Ectoderm. Stem Cells Int 2023; 2023:4547875. [PMID: 37333060 PMCID: PMC10276766 DOI: 10.1155/2023/4547875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 05/04/2023] [Accepted: 05/23/2023] [Indexed: 06/20/2023] Open
Abstract
Since the discovery of mesenchymal stem cells (MSCs) in the 1970s, they have been widely used in the treatment of a variety of diseases because of their wide sources, strong differentiation potential, rapid expansion in vitro, low immunogenicity, and so on. At present, most of the related research is on mesoderm-derived MSCs (M-MSCs) such as bone marrow MSCs and adipose-derived MSCs. As a type of MSC, ectoderm-derived MSCs (E-MSCs) have a stronger potential for self-renewal, multidirectional differentiation, and immunomodulation and have more advantages than M-MSCs in some specific conditions. This paper analyzes the relevant research development of E-MSCs compared with that of M-MSCs; summarizes the extraction, discrimination and culture, biological characteristics, and clinical application of E-MSCs; and discusses the application prospects of E-MSCs. This summary provides a theoretical basis for the better application of MSCs from both ectoderm and mesoderm in the future.
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Affiliation(s)
- Zhenning Wang
- Medical School of Chinese PLA, Beijing 100853, China
- Department of Orthodontics, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Meng Huang
- Medical School of Chinese PLA, Beijing 100853, China
- Department of Orthodontics, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Yu Zhang
- Medical School of Chinese PLA, Beijing 100853, China
- Department of Orthodontics, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Xiaoxia Jiang
- Beijing Institute of Basic Medical Sciences, Beijing 100850, China
| | - Lulu Xu
- Department of Orthodontics, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
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13
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Zhao J, Zhou YH, Zhao YQ, Gao ZR, Ouyang ZY, Ye Q, Liu Q, Chen Y, Tan L, Zhang SH, Feng Y, Hu J, Dusenge MA, Feng YZ, Guo Y. Oral cavity-derived stem cells and preclinical models of jaw-bone defects for bone tissue engineering. Stem Cell Res Ther 2023; 14:39. [PMID: 36927449 PMCID: PMC10022059 DOI: 10.1186/s13287-023-03265-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Accepted: 03/06/2023] [Indexed: 03/18/2023] Open
Abstract
BACKGROUND Jaw-bone defects caused by various diseases lead to aesthetic and functional complications, which can seriously affect the life quality of patients. Current treatments cannot fully meet the needs of reconstruction of jaw-bone defects. Thus, the research and application of bone tissue engineering are a "hot topic." As seed cells for engineering of jaw-bone tissue, oral cavity-derived stem cells have been explored and used widely. Models of jaw-bone defect are excellent tools for the study of bone defect repair in vivo. Different types of bone defect repair require different stem cells and bone defect models. This review aimed to better understand the research status of oral and maxillofacial bone regeneration. MAIN TEXT Data were gathered from PubMed searches and references from relevant studies using the search phrases "bone" AND ("PDLSC" OR "DPSC" OR "SCAP" OR "GMSC" OR "SHED" OR "DFSC" OR "ABMSC" OR "TGPC"); ("jaw" OR "alveolar") AND "bone defect." We screened studies that focus on "bone formation of oral cavity-derived stem cells" and "jaw bone defect models," and reviewed the advantages and disadvantages of oral cavity-derived stem cells and preclinical model of jaw-bone defect models. CONCLUSION The type of cell and animal model should be selected according to the specific research purpose and disease type. This review can provide a foundation for the selection of oral cavity-derived stem cells and defect models in tissue engineering of the jaw bone.
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Affiliation(s)
- Jie Zhao
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Ying-Hui Zhou
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.,National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Ya-Qing Zhao
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Zheng-Rong Gao
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Ze-Yue Ouyang
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Qin Ye
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Qiong Liu
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Yun Chen
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Li Tan
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Shao-Hui Zhang
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Yao Feng
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Jing Hu
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Marie Aimee Dusenge
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Yun-Zhi Feng
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.
| | - Yue Guo
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.
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14
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Moeenzade N, Naseri M, Osmani F, Emadian Razavi F. Dental pulp stem cells for reconstructing bone defects: A systematic review and meta-analysis. J Dent Res Dent Clin Dent Prospects 2022; 16:204-220. [PMID: 37560493 PMCID: PMC10407871 DOI: 10.34172/joddd.2022.034] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 12/02/2022] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND Bone reconstruction with appropriate quality and quantity for dental implant replacement in the alveolar ridge is a challenge in dentistry. As dental pulp stem cells (DPSCs) could be a new perspective in bone regeneration in the future, this study investigated the bone regeneration process by DPSCs. METHODS Electronic searches for articles in the PubMed, EMBASE, and Scopus databases were completed until 21 April 2022. The most important inclusion criteria for selecting in vivo studies reporting quantitative data based on new bone volume and new bone area. The quality assessment was performed based on Cochrane's checklist. RESULTS After the title, abstract, and full-text screening of 762 studies, 23 studies were included. A meta-analysis of 70 studies that reported bone regeneration based on new bone area showed a statistically significant favorable influence on bone tissue regeneration compared to the control groups (P<0.00001, standardized mean difference [SMD]=2.40, 95% CI: 1.55‒3.26; I2=83%). Also, the meta-analysis of 14 studies that reported new bone regeneration based on bone volume showed a statistically significant favorable influence on bone tissue regeneration compared to the control groups (P=0.0003, SMD=1.85, 95% CI: 0.85‒2.85; I2=84%). CONCLUSION This systematic review indicated that DPSCs in tissue regeneration therapy significantly affected bone tissue complex regeneration. However, more and less diverse preclinical studies will enable more powerful meta-analyses in the future.
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Affiliation(s)
- Neda Moeenzade
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Mohsen Naseri
- Cellular and Molecular Research Center, Department of Molecular Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Fereshteh Osmani
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Fariba Emadian Razavi
- Clinical Research Development Unit, School of Dentistry, Birjand University of Medical Sciences, Birjand, Iran
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15
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Lee SH, Kim CH, Yoon JY, Choi EJ, Kim MK, Yoon JU, Kim HY, Kim EJ. Lidocaine intensifies the anti-osteogenic effect on inflammation-induced human dental pulp stem cells via mitogen-activated protein kinase inhibition. J Dent Sci 2022. [DOI: 10.1016/j.jds.2022.11.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
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16
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Nadine S, Fernandes IJ, Correia CR, Mano JF. Close-to-native bone repair via tissue-engineered endochondral ossification approaches. iScience 2022; 25:105370. [PMID: 36339269 PMCID: PMC9626746 DOI: 10.1016/j.isci.2022.105370] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
In order to solve the clinical challenges related to bone grafting, several tissue engineering (TE) strategies have been proposed to repair critical-sized defects. Generally, the classical TE approaches are designed to promote bone repair via intramembranous ossification. Although promising, strategies that direct the osteogenic differentiation of mesenchymal stem/stromal cells are usually characterized by a lack of functional vascular supply, often resulting in necrotic cores. A less explored alternative is engineering bone constructs through a cartilage-mediated approach, resembling the embryological process of endochondral ossification. The remodeling of an intermediary hypertrophic cartilaginous template triggers vascular invasion and bone tissue deposition. Thus, employing this knowledge can be a promising direction for the next generation of bone TE constructs. This review highlights the most recent biomimetic strategies for applying endochondral ossification in bone TE while discussing the plethora of cell types, culture conditions, and biomaterials essential to promote a successful bone regeneration process.
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17
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Demant S, Schoenmaker T, van Erck SMG, Dabelsteen S, de Vries TJ, Bjørndal L. Intra-pulpal connective tissue formation and the advanced carious lesion: Is chondrogenesis and heterotopic ossification a response to pulpal inflammation? Int Endod J 2022; 55:1212-1224. [PMID: 36056458 PMCID: PMC9826515 DOI: 10.1111/iej.13821] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 08/16/2022] [Accepted: 08/17/2022] [Indexed: 01/11/2023]
Abstract
AIMS (a) The aim of this study was to investigate both the formation of dense connective tissue within the dental pulp, and its association with pulpal inflammation in teeth with advanced carious lesions; and (b) to investigate in vitro whether inflammation affects the expression of markers related to chondrogenesis/osteogenesis in pulp cells. MATERIALS AND METHODS Radiology and Histology: Forty-six teeth with advanced carious lesions were radiographically investigated for intra-pulpal radiodense structures. Specimens were processed for histology and stained with haematoxylin/eosin and proteoglycan-specific stains. The intra-pulpal connective tissue was scored as pulp stones or ectopic connective tissue. Cell culture: pulpal cells from human third molars (n = 5) were cultured in chondrogenic medium +/- TLR2/4 agonists. Expression of the genes IL6, TLR2/4, SOX9, COL1A1, COL2A1, TGFB1, RUNX2 and ALPL was assessed by qPCR. Proteoglycan content within cultures was assessed spectrophotometrically. RESULTS Radiodense structures were discovered in about half of all pulps. They were associated with ectopic connective tissue (χ2 = 8.932, p = .004, OR = 6.80, 95% CI: [1.84, 25.19]) and with pulp stones (χ2 = 12.274, df = 1, p < .001, OR = 22.167, 95% CI: [2.57, 200.00]). The morphology of the ectopic tissue resembled cartilage and was associated with inflammatory infiltration of the pulp (χ2 = 10.148, p = .002, OR = 17.77, 95% CI: [2.05, 154.21]). After continuous stimulation of cultured cells with TLR2/4 agonists, the expression of two inflammatory markers increased: IL6 at Days 7 (p = .020) and 14 (p = .008); TLR2 at Days 7 (p = .023) and 14 (p = .009). Similarly, expression of chondrogenic markers decreased: SOX9 at Day 14 (p = .035) and TGFB1 at Day 7 (p = .004), and the osteogenic marker COL1A1 at Day 7 (p = .007). Proteoglycan content did not differ between unstimulated and stimulated cells. CONCLUSIONS Ectopic connective tissue resembling cartilage can form in teeth affected by advanced carious lesions. This tissue type is radiographically visible and is associated with inflammatory infiltration of the pulp. Although TLR2/4 agonists led to an inflammatory response in cell culture of pulp cells, the effect on the expression of osteogenic/chondrogenic markers was limited, suggesting that immune cells are needed for connective tissue formation in vivo.
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Affiliation(s)
- Sune Demant
- Section of Cariology and Endodontics, Department of Odontology, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark,Section of Oral Biology and Immunopathology, Department of Odontology, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark,Department of Endodontics, Academic Center for Dentistry Amsterdam (ACTA)University of Amsterdam and Vrije UniversiteitAmsterdamThe Netherlands
| | - Ton Schoenmaker
- Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA)University of Amsterdam and Vrije UniversiteitAmsterdamThe Netherlands
| | - Sophie M. G. van Erck
- Department of Endodontics, Academic Center for Dentistry Amsterdam (ACTA)University of Amsterdam and Vrije UniversiteitAmsterdamThe Netherlands
| | - Sally Dabelsteen
- Section of Oral Biology and Immunopathology, Department of Odontology, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
| | - Teun J. de Vries
- Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA)University of Amsterdam and Vrije UniversiteitAmsterdamThe Netherlands
| | - Lars Bjørndal
- Section of Cariology and Endodontics, Department of Odontology, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
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18
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DPSCs Protect Architectural Integrity and Alleviate Intervertebral Disc Degeneration by Regulating Nucleus Pulposus Immune Status. Stem Cells Int 2022; 2022:7590337. [PMID: 36299466 PMCID: PMC9590116 DOI: 10.1155/2022/7590337] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 09/17/2022] [Accepted: 09/20/2022] [Indexed: 11/23/2022] Open
Abstract
Intervertebral disc (IVD) degeneration is the primary cause for low back pain that has a high prevalence in modern society and poses enormous economic burden on patients. Few effective therapeutic strategies are available for IVD degeneration treatment. To understand the biological effects of dental pulp stem cells (DPSCs) on nucleus pulposus (NP) cells, we carried out RNA sequencing, bioinformatic analysis which unveiled gene expression differences, and pathway variation in primarily isolated patients' NP cells after treatment with DPSCs supernatant. Western blot and immunofluorescence were used to verify these molecular alterations. Besides, to evaluate the therapeutic effect of DPSCs in IVD degeneration treatment, DPSCs were injected into a degeneration rat model in situ, with treatment outcome measured by micro-CT and histological analysis. RNA sequencing and in vitro experiments demonstrated that DPSCs supernatant could downregulate NP cells' inflammation-related NF-κB and JAK-STAT pathways, reduce IL-6 production, increase collagen II expression, and mitigate apoptosis. In vivo results showed that DPSCs treatment protected the integrity of the disc structure, alleviated extracellular matrix degradation, and increased collagen fiber expression. In this study, we verified the therapeutic effect of DPSCs in an IVD degeneration rat model and elucidated the underlying molecular mechanism of DPSCs treatment, which provides a foundation for the application of DPSCs in IVD degeneration treatment.
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19
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Mohammed EEA, Beherei HH, El-Zawahry M, Farrag ARH, Kholoussi N, Helwa I, Mabrouk M, Abdel Aleem AK. Osteogenic enhancement of modular ceramic nanocomposites impregnated with human dental pulp stem cells: an approach for bone repair and regenerative medicine. J Genet Eng Biotechnol 2022; 20:123. [PMID: 35976537 PMCID: PMC9385929 DOI: 10.1186/s43141-022-00387-4] [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: 02/25/2022] [Accepted: 06/14/2022] [Indexed: 11/24/2022]
Abstract
Background/aim Human dental pulp-derived mesenchymal stem cells (hDP-MSCs) are a promising source of progenitor cells for bone tissue engineering. Nanocomposites made of calcium phosphate especially hydroxyapatite (HA) offer an impressive solution for orthopedic and dental implants. The combination of hDP-MSCs and ceramic nanocomposites has a promising therapeutic potential in regenerative medicine. Despite the calcium phosphate hydroxyapatite (HA)-based nanocomposites offer a good solution for orthopedic and dental implants, the heavy load-bearing clinical applications require higher mechanical strength, which is not of the HA’ properties that have low mechanical strength. Herein, the outcomes of using fabricated ceramic nanocomposites of hydroxyapatite/titania/calcium silicate mixed at different ratios (C1, C2, and C3) and impregnated with hDP-MSCs both in in vitro cultures and rabbit model of induced tibial bone defect were investigated. Our aim is to find out a new approach that would largely enhance the osteogenic differentiation of hDP-MSCs and has a therapeutic potential in bone regeneration. Subjects and methods Human DP-MSCs were isolated from the dental pulp of the third molar and cultured in vitro. Alizarin Red staining was performed at different time points to assess the osteogenic differentiation. Flow cytometer was used to quantify the expression of hDP-MSCs unique surface markers. Rabbits were used as animal models to evaluate the therapeutic potential of osteogenically differentiated hDP-MSCs impregnated with ceramic nanocomposites of hydroxyapatite/tatiana/calcium silicate (C1, C2, and C3). Histopathological examination and scanning electron microscopy (SEM) were performed to evaluate bone healing potential in the rabbit induced tibial defects three weeks post-transplantation. Results The hDP-MSCs showed high proliferative and osteogenic potential in vitro culture. Their osteogenic differentiation was accelerated by the ceramic nanocomposites’ scaffold and revealed bone defect’s healing in transplanted rabbit groups compared to control groups. Histopathological and SEM analysis of the transplanted hDP-MSCs/ceramic nanocomposites showed the formation of new bone filling in the defect area 3 weeks post-implantation. Accelerate osseointegration and enhancement of the bone-bonding ability of the prepared nanocomposites were also confirmed by SEM. Conclusions The results strongly suggested that ceramic nanocomposites of hydroxyapatite/ titania /calcium silicate (C1, C2, and C3) associated with hDP-MSCs have a therapeutic potential in bone healing in a rabbit model. Hence, the combined osteogenic system presented here is recommended for application in bone tissue engineering and regenerative medicine.
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Affiliation(s)
- Eman E A Mohammed
- Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt. .,Refractoriness, Ceramics and Building Materials Department, Inorganic Chemical Industries and Mineral Resources Research Institute, National Research Centre, Cairo, Egypt.
| | - Hanan H Beherei
- Fixed and Removable Prosthodontics Department, Oral and Dental Research Institute, National Research Centre, Cairo, Egypt
| | - Mohamed El-Zawahry
- Pathology Department, Medicine and Clinical Studies Research Institute, National Research Centre, Cairo, Egypt
| | - Abdel Razik H Farrag
- Stem Cell Research Group, Medical Research Center of Excellence, National Research Centre, Cairo, Egypt
| | - Naglaa Kholoussi
- Immunogenetics Department, Human Genetics and Genome Research Institute, National Research Centre, National Research Centre, Cairo, Egypt
| | - Iman Helwa
- Immunogenetics Department, Human Genetics and Genome Research Institute, National Research Centre, National Research Centre, Cairo, Egypt
| | - Mostafa Mabrouk
- Fixed and Removable Prosthodontics Department, Oral and Dental Research Institute, National Research Centre, Cairo, Egypt
| | - Alice K Abdel Aleem
- Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.,Refractoriness, Ceramics and Building Materials Department, Inorganic Chemical Industries and Mineral Resources Research Institute, National Research Centre, Cairo, Egypt
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20
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Choi B, Kim JE, Park SO, Kim EY, Oh S, Choi H, Yoon D, Min HJ, Kim HR, Chang EJ. Sphingosine-1-phosphate hinders the osteogenic differentiation of dental pulp stem cells in association with AKT signaling pathways. Int J Oral Sci 2022; 14:21. [PMID: 35459199 PMCID: PMC9033766 DOI: 10.1038/s41368-022-00173-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 02/24/2022] [Accepted: 02/24/2022] [Indexed: 11/16/2022] Open
Abstract
Sphingosine-1-phosphate (S1P) is an important lipid mediator that regulates a diverse range of intracellular cell signaling pathways that are relevant to tissue engineering and regenerative medicine. However, the precise function of S1P in dental pulp stem cells (DPSCs) and its osteogenic differentiation remains unclear. We here investigated the function of S1P/S1P receptor (S1PR)-mediated cellular signaling in the osteogenic differentiation of DPSCs and clarified the fundamental signaling pathway. Our results showed that S1P-treated DPSCs exhibited a low rate of differentiation toward the osteogenic phenotype in association with a marked reduction in osteogenesis-related gene expression and AKT activation. Of note, both S1PR1/S1PR3 and S1PR2 agonists significantly downregulated the expression of osteogenic genes and suppressed AKT activation, resulting in an attenuated osteogenic capacity of DPSCs. Most importantly, an AKT activator completely abrogated the S1P-mediated downregulation of osteoblastic markers and partially prevented S1P-mediated attenuation effects during osteogenesis. Intriguingly, the pro-inflammatory TNF-α cytokine promoted the infiltration of macrophages toward DPSCs and induced S1P production in both DPSCs and macrophages. Our findings indicate that the elevation of S1P under inflammatory conditions suppresses the osteogenic capacity of the DPSCs responsible for regenerative endodontics.
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Affiliation(s)
- Bongkun Choi
- Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.,Stem Cell Immunomodulation Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ji-Eun Kim
- Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.,Stem Cell Immunomodulation Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Si-On Park
- Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.,Stem Cell Immunomodulation Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun-Young Kim
- Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.,Stem Cell Immunomodulation Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Soyoon Oh
- Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.,Stem Cell Immunomodulation Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyuksu Choi
- Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.,Stem Cell Immunomodulation Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dohee Yoon
- Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.,Stem Cell Immunomodulation Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyo-Jin Min
- Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.,Stem Cell Immunomodulation Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyung-Ryong Kim
- Department of Pharmacology, College of Dentistry, Jeonbuk National University, Jeonju, Korea.
| | - Eun-Ju Chang
- Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea. .,Stem Cell Immunomodulation Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. .,Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
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Kwack KH, Lee HW. Clinical Potential of Dental Pulp Stem Cells in Pulp Regeneration: Current Endodontic Progress and Future Perspectives. Front Cell Dev Biol 2022; 10:857066. [PMID: 35478967 PMCID: PMC9035692 DOI: 10.3389/fcell.2022.857066] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 03/18/2022] [Indexed: 12/12/2022] Open
Abstract
Dental caries is a common disease that not only destroys the rigid structure of the teeth but also causes pulp necrosis in severe cases. Once pulp necrosis has occurred, the most common treatment is to remove the damaged pulp tissue, leading to a loss of tooth vitality and increased tooth fragility. Dental pulp stem cells (DPSCs) isolated from pulp tissue exhibit mesenchymal stem cell-like characteristics and are considered ideal candidates for regenerating damaged dental pulp tissue owing to their multipotency, high proliferation rate, and viability after cryopreservation. Importantly, DPSCs do not elicit an allogeneic immune response because they are non-immunogenic and exhibit potent immunosuppressive properties. Here, we provide an up-to-date review of the clinical applicability and potential of DPSCs, as well as emerging trends in the regeneration of damaged pulp tissue. In addition, we suggest the possibility of using DPSCs as a resource for allogeneic transplantation and provide a perspective for their clinical application in pulp regeneration.
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Affiliation(s)
- Kyu Hwan Kwack
- Department of Dentistry, Graduate School, Kyung Hee University, Seoul, South Korea
| | - Hyeon-Woo Lee
- Department of Pharmacology, School of Dentistry, Graduate School, Institute of Oral Biology, Kyung Hee University, Seoul, South Korea
- *Correspondence: Hyeon-Woo Lee,
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22
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Prajwal GS, Jeyaraman N, Kanth V K, Jeyaraman M, Muthu S, Rajendran SNS, Rajendran RL, Khanna M, Oh EJ, Choi KY, Chung HY, Ahn BC, Gangadaran P. Lineage Differentiation Potential of Different Sources of Mesenchymal Stem Cells for Osteoarthritis Knee. Pharmaceuticals (Basel) 2022; 15:386. [PMID: 35455383 PMCID: PMC9028477 DOI: 10.3390/ph15040386] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 03/11/2022] [Accepted: 03/17/2022] [Indexed: 02/05/2023] Open
Abstract
Tissue engineering and regenerative medicine (TERM) have paved a way for treating musculoskeletal diseases in a minimally invasive manner. The regenerative medicine cocktail involves the usage of mesenchymal stem/stromal cells (MSCs), either uncultured or culture-expanded cells along with growth factors, cytokines, exosomes, and secretomes to provide a better regenerative milieu in degenerative diseases. The successful regeneration of cartilage depends on the selection of the appropriate source of MSCs, the quality, quantity, and frequency of MSCs to be injected, and the selection of the patient at an appropriate stage of the disease. However, confirmation on the most favorable source of MSCs remains uncertain to clinicians. The lack of knowledge in the current cellular treatment is uncertain in terms of how beneficial MSCs are in the long-term or short-term (resolution of pain) and improved quality of life. Whether MSCs treatments have any superiority, exists due to sources of MSCs utilized in their potential to objectively regenerate the cartilage at the target area. Many questions on source and condition remain unanswered. Hence, in this review, we discuss the lineage differentiation potentials of various sources of MSCs used in the management of knee osteoarthritis and emphasize the role of tissue engineering in cartilage regeneration.
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Affiliation(s)
- Gollahalli Shivashankar Prajwal
- Research Fellow, Fellowship in Orthopaedic Rheumatology (FEIORA), Dr. Ram Manohar Lohiya National Law University, Lucknow 226010, Uttar Pradesh, India; (G.S.P.); (N.J.)
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 110048, Uttar Pradesh, India; (S.M.); (M.K.)
- Department of Orthopaedics, Mallika Spine Centre, Guntur 522001, Andhra Pradesh, India
| | - Naveen Jeyaraman
- Research Fellow, Fellowship in Orthopaedic Rheumatology (FEIORA), Dr. Ram Manohar Lohiya National Law University, Lucknow 226010, Uttar Pradesh, India; (G.S.P.); (N.J.)
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 110048, Uttar Pradesh, India; (S.M.); (M.K.)
- Department of Orthopaedics, Atlas Hospitals, Tiruchirappalli 620002, Tamil Nadu, India
| | - Krishna Kanth V
- Department of Orthopaedics, Government Medical College, Mahabubabad 506104, Telangana, India;
| | - Madhan Jeyaraman
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 110048, Uttar Pradesh, India; (S.M.); (M.K.)
- Department of Orthopaedics, Faculty of Medicine—Sri Lalithambigai Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600095, Tamil Nadu, India
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201306, Uttar Pradesh, India
- Orthopaedic Research Group, Coimbatore 641001, Tamil Nadu, India
| | - Sathish Muthu
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 110048, Uttar Pradesh, India; (S.M.); (M.K.)
- Department of Orthopaedics, Government Medical College, Mahabubabad 506104, Telangana, India;
- Department of Orthopaedics, Faculty of Medicine—Sri Lalithambigai Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600095, Tamil Nadu, India
- Orthopaedic Research Group, Coimbatore 641001, Tamil Nadu, India
| | - Sree Naga Sowndary Rajendran
- Department of Medicine, Sri Venkateshwaraa Medical College Hospital and Research Centre, Puducherry 605102, Puducherry, India;
| | - Ramya Lakshmi Rajendran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
| | - Manish Khanna
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 110048, Uttar Pradesh, India; (S.M.); (M.K.)
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul 624001, Tamil Nadu, India
- Department of Orthopaedics, Prasad Institute of Medical Sciences, Lucknow 226010, Uttar Pradesh, India
| | - Eun Jung Oh
- Department of Plastic and Reconstructive Surgery, CMRI, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea; (E.J.O.); (K.Y.C.); (H.Y.C.)
| | - Kang Young Choi
- Department of Plastic and Reconstructive Surgery, CMRI, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea; (E.J.O.); (K.Y.C.); (H.Y.C.)
| | - Ho Yun Chung
- Department of Plastic and Reconstructive Surgery, CMRI, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea; (E.J.O.); (K.Y.C.); (H.Y.C.)
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Korea
| | - Byeong-Cheol Ahn
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Korea
| | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Korea
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Anitua E, Zalduendo M, Troya M, Erezuma I, Lukin I, Hernáez-Moya R, Orive G. Composite alginate-gelatin hydrogels incorporating PRGF enhance human dental pulp cell adhesion, chemotaxis and proliferation. Int J Pharm 2022; 617:121631. [PMID: 35247496 DOI: 10.1016/j.ijpharm.2022.121631] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 02/15/2022] [Accepted: 02/28/2022] [Indexed: 12/26/2022]
Abstract
The increasing prevalence of tissue injuries is fueling the development of autologous biological treatments for regenerative medicine. Here, we investigated the potential of three different bioinks based on the combination of gelatin and alginate (GA), enriched in either hydroxyapatite (GAHA) or hydroxyapatite and PRGF (GAHAP), as a favorable microenvironment for human dental pulp stem cells (DPSCs). Swelling behaviour, in vitro degradation and mechanical properties of the matrices were evaluated. Morphological and elemental analysis of the scaffolds were also performed along with cytocompatibility studies. The in vitro cell response to the different scaffolds was also assessed. Results showed that all scaffolds presented high swelling capacity, and those that contained HA showed higher Young's modulus. GAHAP had the lowest degradation rate and the highest values of cytocompatibility. Cell adhesion and chemotaxis were significantly increased when PRGF was incorporated to the matrices. GAHA and GAHAP compositions promoted the highest proliferative rate as well as significantly stimulated osteogenic differentiation. In conclusion, the enrichment with PRGF improves the regenerative properties of the composites favouring the development of personalized constructs.
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Affiliation(s)
- Eduardo Anitua
- BTI-Biotechnology Institute, Vitoria, Spain; University Institute for Regenerative Medicine and Oral Implantology - UIRMI (UPV/EHU-Fundación Eduardo Anitua). Vitoria-Gasteiz, Spain.
| | - Mar Zalduendo
- BTI-Biotechnology Institute, Vitoria, Spain; University Institute for Regenerative Medicine and Oral Implantology - UIRMI (UPV/EHU-Fundación Eduardo Anitua). Vitoria-Gasteiz, Spain
| | - María Troya
- BTI-Biotechnology Institute, Vitoria, Spain; University Institute for Regenerative Medicine and Oral Implantology - UIRMI (UPV/EHU-Fundación Eduardo Anitua). Vitoria-Gasteiz, Spain
| | - Itsasne Erezuma
- NanoBioCel Research Group, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN). Vitoria-Gasteiz, Spain
| | - Izeia Lukin
- NanoBioCel Research Group, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN). Vitoria-Gasteiz, Spain
| | - Raquel Hernáez-Moya
- NanoBioCel Research Group, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN). Vitoria-Gasteiz, Spain
| | - Gorka Orive
- University Institute for Regenerative Medicine and Oral Implantology - UIRMI (UPV/EHU-Fundación Eduardo Anitua). Vitoria-Gasteiz, Spain; NanoBioCel Research Group, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN). Vitoria-Gasteiz, Spain; Bioaraba, NanoBioCel Research Group, Vitoria-Gasteiz, Spain.
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Staniowski T, Zawadzka-Knefel A, Skośkiewicz-Malinowska K. Therapeutic Potential of Dental Pulp Stem Cells According to Different Transplant Types. Molecules 2021; 26:7423. [PMID: 34946506 PMCID: PMC8707085 DOI: 10.3390/molecules26247423] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/02/2021] [Accepted: 12/04/2021] [Indexed: 12/13/2022] Open
Abstract
Stem cells are unspecialised cells capable of perpetual self-renewal, proliferation and differentiation into more specialised daughter cells. They are present in many tissues and organs, including the stomatognathic system. Recently, the great interest of scientists in obtaining stem cells from human teeth is due to their easy availability and a non-invasive procedure of collecting the material. Three key components are required for tissue regeneration: stem cells, appropriate scaffold material and growth factors. Depending on the source of the new tissue or organ, there are several types of transplants. In this review, the following division into four transplant types is applied due to genetic differences between the donor and the recipient: xenotransplantation, allotransplantation, autotransplantation and isotransplantation (however, due to the lack of research, type was not included). In vivo studies have shown that Dental Pulp Stem Cells (DPSCs)can form a dentin-pulp complex, nerves, adipose, bone, cartilage, skin, blood vessels and myocardium, which gives hope for their use in various biomedical areas, such as immunotherapy and regenerative therapy. This review presents the current in vivo research and advances to provide new biological insights and therapeutic possibilities of using DPSCs.
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Affiliation(s)
| | - Anna Zawadzka-Knefel
- Department of Conservative Dentistry with Endodontics, Wroclaw Medical University, 50-425 Wrocław, Poland; (T.S.); (K.S.-M.)
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25
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Al Madhoun A, Sindhu S, Haddad D, Atari M, Ahmad R, Al-Mulla F. Dental Pulp Stem Cells Derived From Adult Human Third Molar Tooth: A Brief Review. Front Cell Dev Biol 2021; 9:717624. [PMID: 34712658 PMCID: PMC8545885 DOI: 10.3389/fcell.2021.717624] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 09/15/2021] [Indexed: 12/13/2022] Open
Abstract
The fields of regenerative medicine and stem cell-based tissue engineering have the potential of treating numerous tissue and organ defects. The use of adult stem cells is of particular interest when it comes to dynamic applications in translational medicine. Recently, dental pulp stem cells (DPSCs) have been traced in third molars of adult humans. DPSCs have been isolated and characterized by several groups. DPSCs have promising characteristics including self-renewal capacity, rapid proliferation, colony formation, multi-lineage differentiation, and pluripotent gene expression profile. Nevertheless, genotypic, and phenotypic heterogeneities have been reported for DPSCs subpopulations which may influence their therapeutic potentials. The underlying causes of DPSCs’ heterogeneity remain poorly understood; however, their heterogeneity emerges as a consequence of an interplay between intrinsic and extrinsic cellular factors. The main objective of the manuscript is to review the current literature related to the human DPSCs derived from the third molar, with a focus on their physiological properties, isolation procedures, culture conditions, self-renewal, proliferation, lineage differentiation capacities and their prospective advances use in pre-clinical and clinical applications.
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Affiliation(s)
- Ashraf Al Madhoun
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait.,Department of Animal and Imaging Core Facilities, Dasman Diabetes Institute, Dasman, Kuwait
| | - Sardar Sindhu
- Department of Animal and Imaging Core Facilities, Dasman Diabetes Institute, Dasman, Kuwait.,Department of Immunology and Microbiology, Dasman Diabetes Institute, Dasman, Kuwait
| | - Dania Haddad
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait
| | - Maher Atari
- Biointelligence Technology Systems S.L., Barcelona, Spain
| | - Rasheed Ahmad
- Department of Immunology and Microbiology, Dasman Diabetes Institute, Dasman, Kuwait
| | - Fahd Al-Mulla
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait
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26
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La Noce M, Stellavato A, Vassallo V, Cammarota M, Laino L, Desiderio V, Del Vecchio V, Nicoletti GF, Tirino V, Papaccio G, Schiraldi C, Ferraro GA. Hyaluronan-Based Gel Promotes Human Dental Pulp Stem Cells Bone Differentiation by Activating YAP/TAZ Pathway. Cells 2021; 10:cells10112899. [PMID: 34831122 PMCID: PMC8616223 DOI: 10.3390/cells10112899] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 10/21/2021] [Accepted: 10/22/2021] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Hyaluronans exist in different forms, accordingly with molecular weight and degree of crosslinking. Here, we tested the capability to induce osteogenic differentiation in hDPSCs (human dental pulp stem cells) of three hyaluronans forms: linear pharmaceutical-grade hyaluronans at high and (HHA) low molecular weight (LHA) and hybrid cooperative complexes (HCC), containing both sizes. METHODS hDPSCs were treated with HHA, LHA, HCC for 7, 14 and 21 days. The effects of hyaluronans on osteogenic differentiation were evaluated by qRT-PCR and WB of osteogenic markers and by Alizarin Red S staining. To identify the involved pathway, CD44 was analyzed by immunofluorescence, and YAP/TAZ expression was measured by qRT-PCR. Moreover, YAP/TAZ inhibitor-1 was used, and the loss of function of YAP/TAZ was evaluated by qRT-PCR, WB and immunofluorescence. RESULTS We showed that all hyaluronans improves osteogenesis. Among these, HCC is the main inducer of osteogenesis, along with overexpression of bone related markers and upregulating CD44. We also found that this biological process is subordinate to the activation of YAP/TAZ pathway. CONCLUSIONS We found that HA's molecular weight can have a relevant impact on HA performance for bone regeneration, and we unveil a new molecular mechanism by which HA acts on stem cells.
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Affiliation(s)
- Marcella La Noce
- Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy; (M.L.N.); (A.S.); (V.V.); (M.C.); (V.D.); (V.D.V.); (C.S.)
| | - Antonietta Stellavato
- Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy; (M.L.N.); (A.S.); (V.V.); (M.C.); (V.D.); (V.D.V.); (C.S.)
| | - Valentina Vassallo
- Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy; (M.L.N.); (A.S.); (V.V.); (M.C.); (V.D.); (V.D.V.); (C.S.)
| | - Marcella Cammarota
- Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy; (M.L.N.); (A.S.); (V.V.); (M.C.); (V.D.); (V.D.V.); (C.S.)
| | - Luigi Laino
- Multidisciplinary Department of Medical-Surgical and Dental Specialties, University of Campania “L. Vanvitelli”, Via L. de Crecchio 6, 80138 Naples, Italy; (L.L.); (G.F.N.); (G.A.F.)
| | - Vincenzo Desiderio
- Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy; (M.L.N.); (A.S.); (V.V.); (M.C.); (V.D.); (V.D.V.); (C.S.)
| | - Vitale Del Vecchio
- Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy; (M.L.N.); (A.S.); (V.V.); (M.C.); (V.D.); (V.D.V.); (C.S.)
| | - Giovanni Francesco Nicoletti
- Multidisciplinary Department of Medical-Surgical and Dental Specialties, University of Campania “L. Vanvitelli”, Via L. de Crecchio 6, 80138 Naples, Italy; (L.L.); (G.F.N.); (G.A.F.)
| | - Virginia Tirino
- Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy; (M.L.N.); (A.S.); (V.V.); (M.C.); (V.D.); (V.D.V.); (C.S.)
- Correspondence: (V.T.); (G.P.); Tel.: +39-08-1566-4040 (V.T.); +39-08-1566-6014 (G.P.)
| | - Gianpaolo Papaccio
- Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy; (M.L.N.); (A.S.); (V.V.); (M.C.); (V.D.); (V.D.V.); (C.S.)
- Correspondence: (V.T.); (G.P.); Tel.: +39-08-1566-4040 (V.T.); +39-08-1566-6014 (G.P.)
| | - Chiara Schiraldi
- Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy; (M.L.N.); (A.S.); (V.V.); (M.C.); (V.D.); (V.D.V.); (C.S.)
| | - Giuseppe Andrea Ferraro
- Multidisciplinary Department of Medical-Surgical and Dental Specialties, University of Campania “L. Vanvitelli”, Via L. de Crecchio 6, 80138 Naples, Italy; (L.L.); (G.F.N.); (G.A.F.)
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27
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Lee HN, Liang C, Liao L, Tian WD. Advances in Research on Stem Cell-Based Pulp Regeneration. Tissue Eng Regen Med 2021; 18:931-940. [PMID: 34536210 DOI: 10.1007/s13770-021-00389-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 07/17/2021] [Accepted: 08/18/2021] [Indexed: 02/05/2023] Open
Abstract
Although root canal therapy is the most common and widely used treatment at clinical presentation, there are still some postoperative complications. As cell biology and tissue engineering techniques advance rapidly, the use of biological therapy to regenerate dental pulp has become a new trend; Relevant literatures in recent five years were searched using key words such as "root canal therapy", "Dental pulp stem cells", "Dental pulp regeneration", and "Cell homing" in PubMed, Web of Science, etc; Dental pulp stem cells (DPSCs) have multi-differentiation potential, self-renewal capability, and high proliferative ability. Stem cell-based dental pulp regeneration has emerged as a new research hot spot in clinical therapy. Recently, dental pulp-like structures have been generated by the transplantation of exogenous DPSCs or the induction of homing of endogenous DPSCs. Studies on DPSCs are important and significant for dental pulp regeneration and dental restoration; In this review, the existing clinical treatment methods, dental pulp regeneration, and DPSC research status are revealed, and their application prospects are discussed. The stem cell-based pulp regeneration exerts promising potential in clinical therapy for pulp regeneration.
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Affiliation(s)
- Hua-Nien Lee
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases and Engineering Research Center of Oral Translational Medicine, Ministry of Education and National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610044, China
| | - Cheng Liang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases and Engineering Research Center of Oral Translational Medicine, Ministry of Education and National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610044, China
| | - Li Liao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases and Engineering Research Center of Oral Translational Medicine, Ministry of Education and National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610044, China.
| | - Wei-Dong Tian
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases and Engineering Research Center of Oral Translational Medicine, Ministry of Education and National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610044, China.
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Oral Cavity as a Source of Mesenchymal Stem Cells Useful for Regenerative Medicine in Dentistry. Biomedicines 2021; 9:biomedicines9091085. [PMID: 34572271 PMCID: PMC8469189 DOI: 10.3390/biomedicines9091085] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 08/19/2021] [Accepted: 08/23/2021] [Indexed: 12/17/2022] Open
Abstract
The use of mesenchymal stem cells (MSCs) for regenerative purposes has become common in a large variety of diseases. In the dental and maxillofacial field, there are emerging clinical needs that could benefit from MSC-based therapeutic approaches. Even though MSCs can be isolated from different tissues, such as bone marrow, adipose tissue, etc., and are known for their multilineage differentiation, their different anatomical origin can affect the capability to differentiate into a specific tissue. For instance, MSCs isolated from the oral cavity might be more effective than adipose-derived stem cells (ASCs) for the treatment of dental defects. Indeed, in the oral cavity, there are different sources of MSCs that have been individually proposed as promising candidates for tissue engineering protocols. The therapeutic strategy based on MSCs can be direct, by using cells as components of the tissue to be regenerated, or indirect, aimed at delivering local growth factors, cytokines, and chemokines produced by the MSCs. Here, the authors outline the major sources of mesenchymal stem cells attainable from the oral cavity and discuss their possible usage in some of the most compelling therapeutic frontiers, such as periodontal disease and dental pulp regeneration.
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29
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Characteristics, Classification, and Application of Stem Cells Derived from Human Teeth. Stem Cells Int 2021; 2021:8886854. [PMID: 34194509 PMCID: PMC8184333 DOI: 10.1155/2021/8886854] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 02/12/2021] [Accepted: 05/07/2021] [Indexed: 12/31/2022] Open
Abstract
Since mesenchymal stem cells derived from human teeth are characterized as having the properties of excellent proliferation, multilineage differentiation, and immune regulation. Dental stem cells exhibit fibroblast-like microscopic appearance and express mesenchymal markers, embryonic markers, and vascular markers but do not express hematopoietic markers. Dental stem cells are a mixed population with different sensitive markers, characteristics, and therapeutic effects. Single or combined surface markers are not only helpful for understanding the subpopulation of mixed stem cell populations according to cell function but also for improving the stable treatment effect of dental stem cells. Focusing on the discovery and characterization of stem cells isolated from human teeth over the past 20 years, this review outlines the effect of marker sorting on cell proliferation and differentiation ability and the assessment of the clinical application potential. Classified dental stem cells from markers and functional molecules can solve the problem of heterogeneity and ensure the efficacy of cell therapy strategies including dentistry, neurologic diseases, bone repair, and tissue engineering.
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30
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The Selective Histone Deacetylase Inhibitor MI192 Enhances the Osteogenic Differentiation Efficacy of Human Dental Pulp Stromal Cells. Int J Mol Sci 2021; 22:ijms22105224. [PMID: 34069280 PMCID: PMC8156347 DOI: 10.3390/ijms22105224] [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: 04/21/2021] [Accepted: 05/12/2021] [Indexed: 12/14/2022] Open
Abstract
The use of human dental pulp stromal cells (hDPSCs) has gained increasing attention as an alternative stem cell source for bone tissue engineering. The modification of the cells' epigenetics has been found to play an important role in regulating differentiation, with the inhibition of histone deacetylases 3 (HDAC3) being linked to increased osteogenic differentiation. This study aimed to induce epigenetic reprogramming using the HDAC2 and 3 selective inhibitor, MI192 to promote hDPSCs osteogenic capacity for bone regeneration. MI192 treatment caused a time-dose-dependent change in hDPSC morphology and reduction in viability. Additionally, MI192 successfully augmented hDPSC epigenetic functionality, which resulted in increased histone acetylation and cell cycle arrest at the G2/M phase. MI192 pre-treatment exhibited a dose-dependent effect on hDPSCs alkaline phosphatase activity. Quantitative PCR and In-Cell Western further demonstrated that MI192 pre-treatment significantly upregulated hDPSCs osteoblast-related gene and protein expression (alkaline phosphatase, bone morphogenic protein 2, type I collagen and osteocalcin) during osteogenic differentiation. Importantly, MI192 pre-treatment significantly increased hDPSCs extracellular matrix collagen production and mineralisation. As such, for the first time, our findings show that epigenetic reprogramming with the HDAC2 and 3 selective inhibitor MI192 accelerates the osteogenic differentiation of hDPSCs, demonstrating the considerable utility of this MSCs engineering approach for bone augmentation strategies.
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Bouland C, Philippart P, Dequanter D, Corrillon F, Loeb I, Bron D, Lagneaux L, Meuleman N. Cross-Talk Between Mesenchymal Stromal Cells (MSCs) and Endothelial Progenitor Cells (EPCs) in Bone Regeneration. Front Cell Dev Biol 2021; 9:674084. [PMID: 34079804 PMCID: PMC8166285 DOI: 10.3389/fcell.2021.674084] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 04/23/2021] [Indexed: 12/14/2022] Open
Abstract
Bone regeneration is a complex, well-orchestrated process based on the interactions between osteogenesis and angiogenesis, observed in both physiological and pathological situations. However, specific conditions (e.g., bone regeneration in large quantity, immunocompromised regenerative process) require additional support. Tissue engineering offers novel strategies. Bone regeneration requires a cell source, a matrix, growth factors and mechanical stimulation. Regenerative cells, endowed with proliferation and differentiation capacities, aim to recover, maintain, and improve bone functions. Vascularization is mandatory for bone formation, skeletal development, and different osseointegration processes. The latter delivers nutrients, growth factors, oxygen, minerals, etc. The development of mesenchymal stromal cells (MSCs) and endothelial progenitor cells (EPCs) cocultures has shown synergy between the two cell populations. The phenomena of osteogenesis and angiogenesis are intimately intertwined. Thus, cells of the endothelial line indirectly foster osteogenesis, and conversely, MSCs promote angiogenesis through different interaction mechanisms. In addition, various studies have highlighted the importance of the microenvironment via the release of extracellular vesicles (EVs). These EVs stimulate bone regeneration and angiogenesis. In this review, we describe (1) the phenomenon of bone regeneration by different sources of MSCs. We assess (2) the input of EPCs in coculture in bone regeneration and describe their contribution to the osteogenic potential of MSCs. We discuss (3) the interaction mechanisms between MSCs and EPCs in the context of osteogenesis: direct or indirect contact, production of growth factors, and the importance of the microenvironment via the release of EVs.
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Affiliation(s)
- Cyril Bouland
- Department of Stomatology and Maxillofacial Surgery, Saint-Pierre Hospital, Brussels, Belgium.,Laboratory of Clinical Cell Therapy, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
| | - Pierre Philippart
- Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.,Department of Stomatology and Maxillofacial Surgery, IRIS South Hospital, Brussels, Belgium
| | - Didier Dequanter
- Department of Stomatology and Maxillofacial Surgery, Saint-Pierre Hospital, Brussels, Belgium.,Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium
| | - Florent Corrillon
- Laboratory of Clinical Cell Therapy, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
| | - Isabelle Loeb
- Department of Stomatology and Maxillofacial Surgery, Saint-Pierre Hospital, Brussels, Belgium.,Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium
| | - Dominique Bron
- Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.,Department of Hematology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
| | - Laurence Lagneaux
- Laboratory of Clinical Cell Therapy, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
| | - Nathalie Meuleman
- Laboratory of Clinical Cell Therapy, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium.,Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.,Department of Hematology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
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The Effects of Cryogenic Storage on Human Dental Pulp Stem Cells. Int J Mol Sci 2021; 22:ijms22094432. [PMID: 33922674 PMCID: PMC8122943 DOI: 10.3390/ijms22094432] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 04/19/2021] [Accepted: 04/21/2021] [Indexed: 12/11/2022] Open
Abstract
Dental pulp stem cells (DPSCs) are a type of easily accessible adult mesenchymal stem cell. Due to their ease of access, DPSCs show great promise in regenerative medicine. However, the tooth extractions from which DPSCs can be obtained are usually performed at a period of life when donors would have no therapeutic need of them. For this reason, it is imperative that successful stem cell storage techniques are employed so that these cells remain viable for future use. Any such techniques must result in high post-thaw stem cell recovery without compromising stemness, proliferation, or multipotency. Uncontrolled-rate freezing is not a technically or financially demanding technique compared to expensive and laborious controlled-rate freezing techniques. This study was aimed at observing the effect of uncontrolled-rate freezing on DPSCs stored for 6 and 12 months. Dimethyl sulfoxide at a concentration of 10% was used as a cryoprotective agent. Various features such as shape, proliferation capacity, phenotype, and multipotency were studied after DPSC thawing. The DPSCs did not compromise their stemness, viability, proliferation, or differentiating capabilities, even after one year of cryopreservation at −80 °C. After thawing, they retained their stemness markers and low-level expression of hematopoietic markers. We observed a size reduction in recovery DPSCs after one year of storage. This observation indicates that DPSCs can be successfully used in potential clinical applications, even after a year of uncontrolled cryopreservation.
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Imanishi Y, Hata M, Matsukawa R, Aoyagi A, Omi M, Mizutani M, Naruse K, Ozawa S, Honda M, Matsubara T, Takebe J. Efficacy of extracellular vesicles from dental pulp stem cells for bone regeneration in rat calvarial bone defects. Inflamm Regen 2021; 41:12. [PMID: 33853679 PMCID: PMC8048358 DOI: 10.1186/s41232-021-00163-w] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 03/30/2021] [Indexed: 12/27/2022] Open
Abstract
Background Extracellular vesicles (EVs) are known to be secreted by various cells. In particular, mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have tissue repair capacity and anti-inflammatory properties. Dental pulp stem cells (DPSCs), which are MSCs isolated from pulp tissue, are less invasive to the body than other MSCs and can be collected from young individuals. In this study, we investigated the efficacy of EVs secreted by DPSCs (DPSC-EVs) for bone formation. Methods DPSC-EVs were isolated from the cell culture medium of DPSCs. DPSC-EVs were unilaterally injected along with collagen (COL), beta-tricalcium phosphate (β-TCP) or hydroxyapatite (HA) into rat calvarial bone defects. The effects of DPSC-EVs were analyzed by micro-computed tomography (micro-CT) and histological observation. Results Micro-CT showed that administration of DPSC-EVs with the abovementioned scaffolds resulted in bone formation in the periphery of the defects. DPSC-EVs/COL specifically resulted in bone formation in the center of the defects. Histological observation revealed that DPSC-EVs/COL promoted new bone formation. Administration of DPSC-EVs/COL had almost the same effect on the bone defect site as transplantation of DPSCs/COL. Conclusions These results suggest that DPSC-EVs may be effective tools for bone tissue regeneration.
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Affiliation(s)
- Yuka Imanishi
- Department of Removable Prosthodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, 464-8651, Japan
| | - Masaki Hata
- Department of Removable Prosthodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, 464-8651, Japan.
| | - Ryohei Matsukawa
- Department of Removable Prosthodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, 464-8651, Japan
| | - Atsushi Aoyagi
- Department of Removable Prosthodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, 464-8651, Japan
| | - Maiko Omi
- Department of Removable Prosthodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, 464-8651, Japan
| | - Makoto Mizutani
- Department of Oral Anatomy, School of Dentistry, Aichi Gakuin University, Nagoya, Japan
| | - Keiko Naruse
- Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan
| | - Shogo Ozawa
- Department of Removable Prosthodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, 464-8651, Japan
| | - Masaki Honda
- Department of Oral Anatomy, School of Dentistry, Aichi Gakuin University, Nagoya, Japan
| | - Tatsuaki Matsubara
- Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan
| | - Jun Takebe
- Department of Removable Prosthodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, 464-8651, Japan
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AlHindi M, Philip MR. Osteogenic differentiation potential and quantification of fresh and cryopreserved dental follicular stem cells-an in vitro analysis. J Stem Cells Regen Med 2021; 17:28-34. [PMID: 34434005 PMCID: PMC8372412 DOI: 10.46582/jsrm.1701004] [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: 11/04/2020] [Accepted: 02/23/2021] [Indexed: 11/19/2022]
Abstract
Purpose: To isolate and characterize mesenchymal stem cells of dental follicle from fresh and cryopreserved samples and to test any significant difference in their osteogenic differentiation potential by using digital imaging software. We also investigated whether the cryoprotectant used and its concentration is able to maintain cell count and viability. Methods: Mesenchymal stem cells (MSCs) were isolated from dental follicle of impacted third molars. The osteogenic differentiation potential of dental follicle stem cells was assessed using alizarin red and alkaline phosphatase staining followed by digital imaging quantification of the stains. Results: Dental follicle cells have shown typical characterisation by exhibiting the stem cell stromal markers and hematopoietic markers, but there was variance in the percentage of expression in fresh and cryopreserved samples. There was considerable osteogenic differentiation potential in the fresh sample compared to cryopreserved sample. The cell count and viability were preserved in both samples. Conclusions: The results in the study have shown wide variation of osteogenic differentiation potential in fresh and cryopreserved samples. Also, the cryoprotectant was found to be effective in its purpose at the specified concentration.
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Affiliation(s)
- Maryam AlHindi
- Department of Maxillofacial Surgery, College of Dentistry, King Saud University, Riyadh, PO Box11545, KSA
| | - Manju Roby Philip
- Department of Maxillofacial Surgery, College of Dentistry, King Saud University, Riyadh, PO Box11545, KSA
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Nizami MZI, Nishina Y. Recent Advances in Stem Cells for Dental Tissue Engineering. ENGINEERING MATERIALS FOR STEM CELL REGENERATION 2021:281-324. [DOI: 10.1007/978-981-16-4420-7_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Jamal M, Bashir A, Al-Sayegh M, Huang GTJ. Oral tissues as sources for induced pluripotent stem cell derivation and their applications for neural, craniofacial, and dental tissue regeneration. CELL SOURCES FOR IPSCS 2021:71-106. [DOI: 10.1016/b978-0-12-822135-8.00007-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Dental Mesenchymal Stem/Progenitor Cells: A New Prospect in Regenerative Medicine. Stem Cells 2021. [DOI: 10.1007/978-3-030-77052-5_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Zhang B, Huo S, Cen X, Pan X, Huang X, Zhao Z. circAKT3 positively regulates osteogenic differentiation of human dental pulp stromal cells via miR-206/CX43 axis. Stem Cell Res Ther 2020; 11:531. [PMID: 33298186 PMCID: PMC7726914 DOI: 10.1186/s13287-020-02058-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 11/27/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Human dental pulp stromal cells (hDPSCs) are promising sources of mesenchymal stem cells (MSCs) for bone tissue regeneration. Circular RNAs (circRNAs) have been demonstrated to play critical roles in stem cell osteogenic differentiation. Herein, we aimed to investigate the role of circAKT3 during osteogenesis of hDPSCs and the underlying mechanisms of its function. METHODS We performed circRNA sequencing to investigate the expression profiles of circular RNAs during osteogenesis of hDPSCs. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to detect the expression pattern of circAKT3 and miR-206 in hDPSCs during osteogenesis. We knocked down circAKT3 and interfered the expression of miR-206 to verify their regulatory role in hDPSC osteogenesis. We detected hDPSCs mineralization by alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining and used dual-luciferase reporter assay to validate the direct binding between circAKT3 and miR-206. To investigate in vivo mineralization, we performed subcutaneous transplantation in nude mice and used hematoxylin and eosin, Masson's trichrome, and immunohistochemistry staining. RESULTS Totally, 86 circRNAs were differentially expressed during hDPSC osteogenesis, in which 29 were downregulated while 57 were upregulated. circAKT3 was upregulated while miR-206 was downregulated during hDPSC osteogenesis. Knockdown of circAKT3 inhibited ALP/ARS staining and expression levels of osteogenic genes. circAKT3 directly interacted with miR-206, and the latter one suppressed osteogenesis of hDPSCs. Silencing miR-206 partially reversed the inhibitory effect of circAKT3 knockdown on osteogenesis. Connexin 43 (CX43), which positively regulates osteogenesis of stem cells, was predicted as a target of miR-206, and overexpression or knockdown of miR-206 could correspondingly decrease and increase the expression of CX43. In vivo study showed knockdown of circAKT3 suppressed the formation of mineralized nodules and expression of osteogenic proteins. CONCLUSION During osteogenesis of hDPSCs, circAKT3 could function as a positive regulator by directly sponging miR-206 and arresting the inhibitive effect of miR-206 on CX43 expression.
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Affiliation(s)
- Bo Zhang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, People's Republic of China
| | - Sibei Huo
- Department of Stomatology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders (Chongqing), Chongqing, People's Republic of China
| | - Xiao Cen
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China
- Department of Temporomandibular Joint, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China
| | - Xuefeng Pan
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, People's Republic of China
| | - Xinqi Huang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China.
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, People's Republic of China.
| | - Zhihe Zhao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China.
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, People's Republic of China.
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Perczel-Kovách K, Hegedűs O, Földes A, Sangngoen T, Kálló K, Steward MC, Varga G, Nagy KS. STRO-1 positive cell expansion during osteogenic differentiation: A comparative study of three mesenchymal stem cell types of dental origin. Arch Oral Biol 2020; 122:104995. [PMID: 33278647 DOI: 10.1016/j.archoralbio.2020.104995] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 10/31/2020] [Accepted: 11/16/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Although the osteogenic differentiation potential of mesenchymal stem cells of dental origin is well established, the roles of different marker proteins in this process remain to be clarified. Our aim was to compare the cellular and molecular changes, focusing in particular on mesenchymal stem cell markers, during in vitro osteogenesis in three dental stem cell types: dental follicle stem cells (DFSCs), periodontal ligament stem cells (PDLSCs) and dental pulp stem cells (DPSCs). DESIGN Human DFSCs, PDLSCs and DPSCs were isolated, cultured and their osteogenic differentiation was induced for 3 weeks. Mineralization was assessed by von Kossa staining and calcium concentration measurements. The expression of mesenchymal and osteogenic markers was studied by immunocytochemistry and qPCR techniques. Alkaline phosphatase (ALP) activity and the frequency of STRO-1 positive cells were also quantified. RESULTS The three cultures all showed abundant mineralization, with high calcium content by day 21. The expression of vimentin and nestin was sustained after osteogenic induction. The osteogenic medium induced a considerable elevation of STRO-1 positive cells. By day 7, the ALP mRNA level had increased more than 100-fold in DFSCs, PDLSCs, and DPSCs. Quantitative PCR results indicated dissimilarities of osteoblastic marker levels in the three dental stem cell cultures. CONCLUSIONS DFSCs, PDLSCs and DPSCs have similar functional osteogenic differentiation capacities although their expressional profiles of key osteogenic markers show considerable variations. The STRO-1 positive cell fraction expands during osteogenic differentiation while vimentin and nestin expression remain high. For identification of stemness, functional studies rather than marker expressions are needed.
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Affiliation(s)
- Katalin Perczel-Kovách
- Department of Oral Biology, Semmelweis University, Nagyvárad Square 4. H-1089 Budapest, Hungary.
| | - Orsolya Hegedűs
- Department of Oral Biology, Semmelweis University, Nagyvárad Square 4. H-1089 Budapest, Hungary.
| | - Anna Földes
- Department of Oral Biology, Semmelweis University, Nagyvárad Square 4. H-1089 Budapest, Hungary.
| | - Thanyaporn Sangngoen
- Department of Oral Biology, Semmelweis University, Nagyvárad Square 4. H-1089 Budapest, Hungary.
| | - Karola Kálló
- Department of Oral Biology, Semmelweis University, Nagyvárad Square 4. H-1089 Budapest, Hungary
| | - Martin C Steward
- Department of Oral Biology, Semmelweis University, Nagyvárad Square 4. H-1089 Budapest, Hungary; School of Medical Sciences, University of Manchester, Manchester, United Kingdom.
| | - Gábor Varga
- Department of Oral Biology, Semmelweis University, Nagyvárad Square 4. H-1089 Budapest, Hungary.
| | - Krisztina S Nagy
- Department of Oral Biology, Semmelweis University, Nagyvárad Square 4. H-1089 Budapest, Hungary.
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Shiu ST, Lew WZ, Lee SY, Feng SW, Huang HM. Effects of Sapindus mukorossi Seed Oil on Proliferation, Osteogenetic/Odontogenetic Differentiation and Matrix Vesicle Secretion of Human Dental Pulp Mesenchymal Stem Cells. MATERIALS (BASEL, SWITZERLAND) 2020; 13:E4063. [PMID: 32933188 PMCID: PMC7560370 DOI: 10.3390/ma13184063] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 09/07/2020] [Accepted: 09/11/2020] [Indexed: 12/18/2022]
Abstract
Stem cells have attracted great interest in the development of tissue engineering. However, the self-regeneration and multi-differentiation capabilities of stem cells are easily impaired during cell transplantation. Recent studies have demonstrated that Sapindus mukorossi (S. mukorossi) seed oil has various positive biological effects. However, it is not yet clear whether S. mukorossi seed oil can increase the growth and differentiation of dental pulp mesenchymal stem cells (DPSCs). The aim of this study is to investigate the effects of S. mukorossi seed oil on the proliferation and differentiation of DPSCs. DPSCs with and without S. mukorossi seed oil, respectively, were evaluated and compared. The viabilities of the cells were assessed by MTT tests. The osteogenetic and odontogenetic capacities of the DPSCs were tested using Alizarin red S staining and alkaline phosphatase (ALP) activity assays. In addition, real-time PCR was performed to examine the gene expression of ALP, BMP-2 and DMP-1. Finally, extracellular matrix vesicle secretion was detected via scanning electron microscopy. No significant difference was observed in the viabilities of the DPSCs with and without S. mukorossi seed oil, respectively. However, under osteogenic and odontogenic induction, S. mukorossi seed oil increased the secretion of mineralized nodules and the ALP activity of the DPSCs (p < 0.05). The ALP gene expression of the differentiation-induced DPSCs was also enhanced. Finally, a greater secretion of extracellular matrix vesicles was detected in the DPSCs following odontogenic induction complemented with S. mukorossi seed oil. Overall, the present results show that S. mukorossi seed oil promotes the osteogenic/odontogenic differentiation and matrix vesicle secretion of DPSCs.
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Affiliation(s)
- Shiau-Ting Shiu
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan; (S.-T.S.); (W.-Z.L.); (S.-Y.L.)
- Department of Dentistry, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
| | - Wei-Zhen Lew
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan; (S.-T.S.); (W.-Z.L.); (S.-Y.L.)
| | - Sheng-Yang Lee
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan; (S.-T.S.); (W.-Z.L.); (S.-Y.L.)
- Department of Dentistry, Wan-Fang Medical Center, Taipei Medical University, Taipei 11031, Taiwan
| | - Sheng-Wei Feng
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan; (S.-T.S.); (W.-Z.L.); (S.-Y.L.)
- Division of Prosthodontics, Department of Dentistry, Taipei Medical University Hospital, Taipei 11031, Taiwan
| | - Haw-Ming Huang
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan; (S.-T.S.); (W.-Z.L.); (S.-Y.L.)
- Graduate Institute of Biomedical Optomechatronics, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan
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Yan M, Nada OA, Kluwe L, Gosau M, Smeets R, Friedrich RE. Expansion of Human Dental Pulp Cells In Vitro Under Different Cryopreservation Conditions. In Vivo 2020; 34:2363-2370. [PMID: 32871761 DOI: 10.21873/invivo.12049] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 07/03/2020] [Accepted: 07/06/2020] [Indexed: 01/09/2023]
Abstract
BACKGROUND/AIM To optimize the expansion of human dental pulp cells in vitro by exploring several cryopreservation methodologies. MATERIALS AND METHODS The intra-dental pulp tissues from healthy subjects were extracted and divided into three separate tissue segments, which were randomly divided into the three following groups; the fresh group, the 5% DMSO group, and the 10% DMSO group. In the fresh group, dental pulp cells were directly cultivated as primary cultures, whereas in the DMSO groups, the dental pulp cells were cultivated from cryopreserved pulp tissue segments one month later. RESULTS The cell yield and the time it took for the cells to grow out of the pulp tissue and attach to the culture plate varied among the three groups; the 5% DMSO group was inferior to the fresh group but superior to the 10% DMSO group (p<0.05). Moreover, no differences were found at the 1st passage amongst the three groups regarding the following aspects (p>0.05); colony formation rate and cell survival rate. Furthermore, no differences were noted at the 3rd passage regarding the following aspects (p>0.05); proliferation ability, cell growth curve and surface marker expression of dental pulp cells. CONCLUSION Five percent DMSO may be the most optimal condition for tissue storage to preserve stem cells in situ.
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Affiliation(s)
- Ming Yan
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ola A Nada
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Lan Kluwe
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Martin Gosau
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ralf Smeets
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Reinhard E Friedrich
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Wang W, Yuan C, Liu Z, Geng T, Li X, Wei L, Niu W, Wang P. Characteristic comparison between canine and human dental mesenchymal stem cells for periodontal regeneration research in preclinical animal studies. Tissue Cell 2020; 67:101405. [PMID: 32835938 DOI: 10.1016/j.tice.2020.101405] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 07/04/2020] [Accepted: 07/04/2020] [Indexed: 12/19/2022]
Abstract
The effectiveness of stem cell-based periodontal tissue engineering need to be assessed by preclinical animal studies. Dog models are widely used animal models; however, there are not sufficient data on characterization of canine dental mesenchymal stem cells. Therefore, we aimed to compare the characteristics among canine and human periodontal ligament stem cells and canine and human dental pulp stem cells. Canine periodontal ligament stem cells and dental pulp stem cells showed significantly weaker clonogenic capability, and proliferation and migration capacity, and they displayed lower positive rates for CD90, CD73, CD105, and STRO-1. All of these canine and human cells showed multilineage differentiation potential. After osteogenic induction, the expression of alkaline phosphatase was obviously upregulated in human dental mesenchymal stem cells, but it was not upregulated in canine dental pulp stem cells. Other osteogenic genes, such as runt-related transcription factor 2 and bone morphogenetic protein 2, were upregulated in all induced canine and human cells, but their upregulation occurred later in canine cells. These results confirmed the stem cell properties of canine mesenchymal stem cells, but also suggested that more attention should be paid to the choice of appropriate research approaches, osteogenic gene markers, and time points for the utilization of canine dental mesenchymal stem cells due to their distinct characteristics.
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Affiliation(s)
- Wen Wang
- Xuzhou Stomatological Hospital, No. 130 Huaihai West Road, Xuzhou, 221000, Jiangsu, China; Xuzhou Medical University, No.209 Tongshan Road, Xuzhou, 221000, Jiangsu, China
| | - Changyong Yuan
- Xuzhou Stomatological Hospital, No. 130 Huaihai West Road, Xuzhou, 221000, Jiangsu, China; Xuzhou Medical University, No.209 Tongshan Road, Xuzhou, 221000, Jiangsu, China
| | - Zongxiang Liu
- Xuzhou Stomatological Hospital, No. 130 Huaihai West Road, Xuzhou, 221000, Jiangsu, China; Xuzhou Medical University, No.209 Tongshan Road, Xuzhou, 221000, Jiangsu, China
| | - Tengyu Geng
- Xuzhou Stomatological Hospital, No. 130 Huaihai West Road, Xuzhou, 221000, Jiangsu, China; Xuzhou Medical University, No.209 Tongshan Road, Xuzhou, 221000, Jiangsu, China
| | - Xingjia Li
- Xuzhou Stomatological Hospital, No. 130 Huaihai West Road, Xuzhou, 221000, Jiangsu, China; Xuzhou Medical University, No.209 Tongshan Road, Xuzhou, 221000, Jiangsu, China
| | - Luming Wei
- Xuzhou Stomatological Hospital, No. 130 Huaihai West Road, Xuzhou, 221000, Jiangsu, China; Xuzhou Medical University, No.209 Tongshan Road, Xuzhou, 221000, Jiangsu, China
| | - Wenzhi Niu
- Xuzhou Stomatological Hospital, No. 130 Huaihai West Road, Xuzhou, 221000, Jiangsu, China; Xuzhou Medical University, No.209 Tongshan Road, Xuzhou, 221000, Jiangsu, China.
| | - Penglai Wang
- Xuzhou Stomatological Hospital, No. 130 Huaihai West Road, Xuzhou, 221000, Jiangsu, China; Xuzhou Medical University, No.209 Tongshan Road, Xuzhou, 221000, Jiangsu, China.
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Ledesma-Martínez E, Mendoza-Núñez VM, Santiago-Osorio E. Mesenchymal Stem Cells for Periodontal Tissue Regeneration in Elderly Patients. J Gerontol A Biol Sci Med Sci 2020; 74:1351-1358. [PMID: 30289440 DOI: 10.1093/gerona/gly227] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Indexed: 12/16/2022] Open
Abstract
Mesenchymal stem cell (MSC) grafting is a highly promising alternative strategy for periodontal regeneration in periodontitis, which is one of the primary causes of tooth loss in the elderly. However, aging progressively decreases the proliferative and differentiation potential of MSCs and diminishes their regenerative capacity, which represents a limiting factor for their endogenous use in elderly patients. Therefore, tissue regeneration therapy with MSCs in this age group may require a cellular source without the physiological limitations that MSCs exhibit in aging. In this sense, exogenous or allogeneic MSCs could have a better chance of success in regenerating periodontal tissue in elderly patients. This review examines and synthesizes recent data in support of the use of MSCs for periodontal regenerative therapy in patients. Additionally, we analyze the progress of the therapeutic use of exogenous MSCs in humans.
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Affiliation(s)
- Edgar Ledesma-Martínez
- Haematopoiesis and Leukaemia Laboratory, Research Unit on Cell Differentiation and Cancer, National Autonomous University of Mexico, Mexico City, Mexico
| | | | - Edelmiro Santiago-Osorio
- Haematopoiesis and Leukaemia Laboratory, Research Unit on Cell Differentiation and Cancer, National Autonomous University of Mexico, Mexico City, Mexico
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Pisciotta A, Bertani G, Bertoni L, Di Tinco R, De Biasi S, Vallarola A, Pignatti E, Tupler R, Salvarani C, de Pol A, Carnevale G. Modulation of Cell Death and Promotion of Chondrogenic Differentiation by Fas/FasL in Human Dental Pulp Stem Cells (hDPSCs). Front Cell Dev Biol 2020; 8:279. [PMID: 32500073 PMCID: PMC7242757 DOI: 10.3389/fcell.2020.00279] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 03/31/2020] [Indexed: 01/01/2023] Open
Abstract
Human dental pulp stem cells (hDPSCs) are characterized by high proliferation rate, the multi-differentiation ability and, notably, low immunogenicity and immunomodulatory properties exerted through different mechanisms including Fas/FasL pathway. Despite their multipotency, hDPSCs require particular conditions to achieve chondrogenic differentiation. This might be due to the perivascular localization and the expression of angiogenic marker under standard culture conditions. FasL stimulation was able to promote the early induction of chondrogenic commitment and to lead the differentiation at later times. Interestingly, the expression of angiogenic marker was reduced by FasL stimulation without activating the extrinsic apoptotic pathway in standard culture conditions. In conclusion, these findings highlight the peculiar embryological origin of hDPSCs and provide further insights on their biological properties. Therefore, Fas/FasL pathway not only is involved in determining the immunomodulatory properties, but also is implicated in supporting the chondrogenic commitment of hDPSCs.
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Affiliation(s)
- Alessandra Pisciotta
- Department of Surgery, Medicine Dentistry and Morphological Sciences with Interest in Transplant, University of Modena and Reggio Emilia, Modena, Italy
| | - Giulia Bertani
- Department of Surgery, Medicine Dentistry and Morphological Sciences with Interest in Transplant, University of Modena and Reggio Emilia, Modena, Italy
| | - Laura Bertoni
- Department of Surgery, Medicine Dentistry and Morphological Sciences with Interest in Transplant, University of Modena and Reggio Emilia, Modena, Italy
| | - Rosanna Di Tinco
- Department of Surgery, Medicine Dentistry and Morphological Sciences with Interest in Transplant, University of Modena and Reggio Emilia, Modena, Italy
| | - Sara De Biasi
- Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Antonio Vallarola
- Department of Biomedical, Metabolic and Neural Sciences, Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Modena, Italy
| | - Elisa Pignatti
- Department of Surgery, Medicine Dentistry and Morphological Sciences with Interest in Transplant, University of Modena and Reggio Emilia, Modena, Italy
| | - Rossella Tupler
- Department of Biomedical, Metabolic and Neural Sciences, Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Modena, Italy
| | - Carlo Salvarani
- Rheumatology Unit, Azienda Unitá Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Anto de Pol
- Department of Surgery, Medicine Dentistry and Morphological Sciences with Interest in Transplant, University of Modena and Reggio Emilia, Modena, Italy
| | - Gianluca Carnevale
- Department of Surgery, Medicine Dentistry and Morphological Sciences with Interest in Transplant, University of Modena and Reggio Emilia, Modena, Italy
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Bertassoli BM, Silva GAB, Albergaria JD, Jorge EC. In vitro analysis of the influence of mineralized and EDTA-demineralized allogenous bone on the viability and differentiation of osteoblasts and dental pulp stem cells. Cell Tissue Bank 2020; 21:479-493. [PMID: 32385788 DOI: 10.1007/s10561-020-09834-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 04/07/2020] [Indexed: 01/09/2023]
Abstract
Grafting based on both autogenous and allogenous human bone is widely used to replace areas of critical loss to induce bone regeneration. Allogenous bones have the advantage of unlimited availability from tissue banks. However, their integration into the remaining bone is limited because they lack osteoinduction and osteogenic properties. Here, we propose to induce the demineralization of the allografts to improve these properties by exposing the organic components. Allografts fragments were demineralized in 10% EDTA at pH 7.2 solution. The influence of the EDTA-DAB and MAB fragments was evaluated with respect to the adhesion, growth and differentiation of MC3'T3-E1 osteoblasts, primary osteoblasts and dental pulp stem cells (DPSC). Histomorphological analyses showed that EDTA-demineralized fragments (EDTA-DAB) maintained a bone architecture and porosity similar to those of the mineralized (MAB) samples. BMP4, osteopontin, and collagen III were also preserved. All the cell types adhered, grew and colonized both the MAB and EDTA-DAB biomaterials after 7, 14 and 21 days. However, the osteoblastic cell lines showed higher viability indexes when they were cultivated on the EDTA-DAB fragments, while the MAB fragments induced higher DPSC viability. The improved osteoinductive potential of the EDTA-DAB bone was confirmed by alkaline phosphatase activity and calcium deposition analyses. This work provides guidance for the choice of the most appropriate allograft to be used in tissue bioengineering and for the transport of specific cell lineages to the surgical site.
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Affiliation(s)
| | | | - Juliano Douglas Albergaria
- Laboratório de Biologia Oral E Do Desevolvimento, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, 31270-901, Brazil.
| | - Erika Cristina Jorge
- Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
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Ueda T, Inden M, Ito T, Kurita H, Hozumi I. Characteristics and Therapeutic Potential of Dental Pulp Stem Cells on Neurodegenerative Diseases. Front Neurosci 2020; 14:407. [PMID: 32457568 PMCID: PMC7222959 DOI: 10.3389/fnins.2020.00407] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 04/03/2020] [Indexed: 12/13/2022] Open
Abstract
To evaluate the therapeutic potential of stem cells for neurodegenerative diseases, emphasis should be placed on clarifying the characteristics of the various types of stem cells. Among stem cells, dental pulp stem cells (DPSCs) are a cell population that is rich in cell proliferation and multipotency. It has been reported that transplantation of DPSCs has protective effects against models of neurodegenerative diseases. The protective effects are not only through differentiation into the target cell type for the disease but are also related to trophic factors released from DPSCs. Recently, it has been reported that serum-free culture supernatant of dental pulp stem cell-conditioned medium (DPCM) contains various trophic factors and cytokines and that DPCM is effective for models of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS). Moreover, the use of stem cells from human exfoliated deciduous teeth (SHEDs) has been considered. SHEDs are derived from deciduous teeth that have been disposed of as medical waste. SHEDs have higher differentiation capacity and proliferation ability than DPSCs. In addition, the serum-free culture supernatant of SHEDs (SHED-CM) contains more trophic factors, cytokines, and biometals than DPCM and also promotes neuroprotection. The neuroprotective effect of DPSCs, including those from deciduous teeth, will be used as the seeds of therapeutic drugs for neurodegenerative diseases. SHEDs will be used for further cell therapy of neurodegenerative diseases in the future. In this paper, we focused on the characteristics of DPSCs and their potential for neurodegenerative diseases.
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Affiliation(s)
- Tomoyuki Ueda
- Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, Gifu, Japan
| | - Masatoshi Inden
- Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, Gifu, Japan
| | - Taisei Ito
- Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, Gifu, Japan
| | - Hisaka Kurita
- Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, Gifu, Japan
| | - Isao Hozumi
- Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, Gifu, Japan
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Pisciotta A, Bertoni L, Vallarola A, Bertani G, Mecugni D, Carnevale G. Neural crest derived stem cells from dental pulp and tooth-associated stem cells for peripheral nerve regeneration. Neural Regen Res 2020; 15:373-381. [PMID: 31571644 PMCID: PMC6921350 DOI: 10.4103/1673-5374.266043] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2018] [Accepted: 05/11/2019] [Indexed: 12/15/2022] Open
Abstract
The peripheral nerve injuries, representing some of the most common types of traumatic lesions affecting the nervous system, are highly invalidating for the patients besides being a huge social burden. Although peripheral nervous system owns a higher regenerative capacity than does central nervous system, mostly depending on Schwann cells intervention in injury repair, several factors determine the extent of functional outcome after healing. Based on the injury type, different therapeutic approaches have been investigated so far. Nerve grafting and Schwann cell transplantation have represented the gold standard treatment for peripheral nerve injuries, however these approaches own limitations, such as scarce donor nerve availability and donor site morbidity. Cell based therapies might provide a suitable tool for peripheral nerve regeneration, in fact, the ability of different stem cell types to differentiate towards Schwann cells in combination with the use of different scaffolds have been widely investigated in animal models of peripheral nerve injuries in the last decade. Dental pulp is a promising cell source for regenerative medicine, because of the ease of isolation procedures, stem cell proliferation and multipotency abilities, which are due to the embryological origin from neural crest. In this article we review the literature concerning the application of tooth derived stem cell populations combined with different conduits to peripheral nerve injuries animal models, highlighting their regenerative contribution exerted through either glial differentiation and neuroprotective/neurotrophic effects on the host tissue.
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Affiliation(s)
- Alessandra Pisciotta
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Laura Bertoni
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Antonio Vallarola
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Giulia Bertani
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Daniela Mecugni
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
- Azienda USL - Institute and Health Care (IRCCS) di Reggio Emilia, Reggio Emilia, Italy
| | - Gianluca Carnevale
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
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48
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Omer A, Al-Sharabi N, Qiu Y, Xue Y, Li Y, Fujio M, Mustafa K, Xing Z. Biological responses of dental pulp cells to surfaces modified by collagen 1 and fibronectin. J Biomed Mater Res A 2020; 108:1369-1379. [PMID: 32107841 DOI: 10.1002/jbm.a.36908] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 02/18/2020] [Accepted: 02/24/2020] [Indexed: 01/09/2023]
Abstract
Collagen 1 (COL1) and fibronectin (FN) are extracellular matrix proteins that contribute in cell activity and involve in regulating dental pulp cells (DPCs). The purpose of this study was to investigate the effect of COL1 and FN on the behavior of DPCs. Here, DPCs were grown under three different conditions: COL1 coating, FN coating, and control group without coating. The proliferation and differentiation of DPCs were investigated. DPCs in osteogenic media were able to differentiate into osteoblastic phenotype. The morphological analysis revealed no obvious difference on the shape of cells. Cells had spread well on both coated and noncoated culture plates with slightly more spreading in the coated plates after 24 hr. The MTT analysis did not demonstrate a significant difference at 1 and 3 hr among the groups, but interestingly, the analysis disclosed more cells on the coated plates after longer cultures, which indicated a higher proliferative capacity in response to COL1 and FN. RT-PCR, Western Blotting and mineralization assays did not reveal significant differences between the coated and noncoated surfaces in relation to osteogenic differential potential. Our data suggested that the surface coating of COL1 and FN were able to promote cellular proliferation and the osteogenic differentiation tendency of DPCs was also observed in vitro.
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Affiliation(s)
- Abedelfattah Omer
- School of Stomatology, Lanzhou University, Lanzhou, People's Republic of China.,Centre for Clinical Dental Research, Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Bergen, Norway
| | - Niyaz Al-Sharabi
- Centre for Clinical Dental Research, Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Bergen, Norway
| | - Yingfei Qiu
- School of Stomatology, Lanzhou University, Lanzhou, People's Republic of China
| | - Ying Xue
- Centre for Clinical Dental Research, Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Bergen, Norway
| | - Yi Li
- School of Stomatology, Lanzhou University, Lanzhou, People's Republic of China
| | - Masahito Fujio
- Centre for Clinical Dental Research, Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Bergen, Norway.,Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kamal Mustafa
- Centre for Clinical Dental Research, Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Bergen, Norway
| | - Zhe Xing
- School of Stomatology, Lanzhou University, Lanzhou, People's Republic of China.,Centre for Clinical Dental Research, Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Bergen, Norway
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Wang W, Yuan C, Geng T, Liu Y, Zhu S, Zhang C, Liu Z, Wang P. EphrinB2 overexpression enhances osteogenic differentiation of dental pulp stem cells partially through ephrinB2-mediated reverse signaling. Stem Cell Res Ther 2020; 11:40. [PMID: 31996240 PMCID: PMC6990579 DOI: 10.1186/s13287-019-1540-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 11/19/2019] [Accepted: 12/23/2019] [Indexed: 12/23/2022] Open
Abstract
Background Alveolar bone loss is a frequent occurrence. Dental pulp stem cells (DPSCs) which have invasive accessibility and high osteogenic potential is a promising source for cell-based bone regeneration. EphrinB2 is involved in bone homeostasis and osteogenesis. The aim of this study was to investigate the effect and mechanism of ephrinB2 overexpression on osteogenic differentiation of DPSCs and bone defect repair. Methods EphrinB2 expression was analyzed during osteogenic induction of human DPSCs (hDPSCs). Endogenous ephrinB2 expression in hDPSCs was then upregulated using EfnB2 lentiviral vectors. The effect of ephrinB2 overexpression on osteogenic differentiation capacity of hDPSCs was investigated in vitro, and activation of ephrinB2-EphB4 bidirectional signaling in ephrinB2-overexpressing hDPSCs was detected. In vivo, a canine alveolar bone defect model was established and canine DPSCs (cDPSCs) were cultured, characterized, EfnB2-tranfected, and combined with a PuraMatrix scaffold. Micro-CT analysis was performed to evaluate the therapeutic effect of ephrinB2-overexpressing cDPSCs on bone defect repair. Results EphrinB2 was upregulated after osteogenic induction of hDPSCs. EphrinB2 overexpression enhanced osteogenic differentiation capacity of hDPSCs in vitro. Moreover, p-ephrinB2 instead of p-EphB4 was upregulated by ephrinB2 overexpression, and activation of ephrinB2-mediated reverse signaling promoted osteogenic differentiation of hDPSCs. In a canine bone defect model, ephrinB2 overexpression in cDPSCs significantly improved trabecular bone volume per tissue volume (BV/TV) and trabecular thickness, as demonstrated by radiographic analysis. Conclusions EphrinB2 overexpression enhanced osteogenic potential of DPSCs partially via upregulation of ephrinB2-mediated reverse signaling and effectively promoted alveolar bone defect repair. Electronic supplementary material The online version of this article (10.1186/s13287-019-1540-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Wen Wang
- Affiliated Stomatological Hospital of Xuzhou Medical University, No. 130 Huaihai West Road, Xuzhou, 221000, Jiangsu, China
| | - Changyong Yuan
- Affiliated Stomatological Hospital of Xuzhou Medical University, No. 130 Huaihai West Road, Xuzhou, 221000, Jiangsu, China
| | - Tengyu Geng
- Affiliated Stomatological Hospital of Xuzhou Medical University, No. 130 Huaihai West Road, Xuzhou, 221000, Jiangsu, China
| | - Yi Liu
- Affiliated Stomatological Hospital of Xuzhou Medical University, No. 130 Huaihai West Road, Xuzhou, 221000, Jiangsu, China
| | - Shaoyue Zhu
- Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, 999077, China
| | - Chengfei Zhang
- Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, 999077, China
| | - Zongxiang Liu
- Affiliated Stomatological Hospital of Xuzhou Medical University, No. 130 Huaihai West Road, Xuzhou, 221000, Jiangsu, China.
| | - Penglai Wang
- Affiliated Stomatological Hospital of Xuzhou Medical University, No. 130 Huaihai West Road, Xuzhou, 221000, Jiangsu, China.
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Qu C, Brohlin M, Kingham PJ, Kelk P. Evaluation of growth, stemness, and angiogenic properties of dental pulp stem cells cultured in cGMP xeno-/serum-free medium. Cell Tissue Res 2019; 380:93-105. [PMID: 31889209 DOI: 10.1007/s00441-019-03160-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Accepted: 12/12/2019] [Indexed: 12/15/2022]
Abstract
This study was aimed to investigate the effects of cGMP xeno-/serum-free medium (XSF, Irvine Scientific) on the properties of human dental pulp stem cells (DPSCs). DPSCs, from passage 2, were cultured in XSF or fetal bovine serum (FBS)-supplemented medium, and sub-cultured up to passage 8. Cumulative population doublings (PDs) and the number of colony-forming-units (CFUs) were determined. qRT-PCR, ELISA, and in vitro assays were used to assess angiogenic capacity. Flow cytometry was used to measure CD73, CD90, and CD105 expression. Differentiation into osteo-, adipo-, and chondrogenic cell lineages was performed. DPSCs showed more elongated morphology, a reduced rate of proliferation at later passages, and lower CFU counts in XSF compared with FBS. Expression of angiogenic factors at the gene and protein levels varied in the two media and with passage number, but cells grown in XSF had more in vitro angiogenic activity. The majority of early and late passage DPSCs cultured in XSF expressed CD73 and CD90. In contrast, the percentage of CD105 positive DPSCs in XSF medium was significantly lower with increased passage whereas the majority of cells cultured in FBS were CD105 positive. Switching XSF-cultured DPSCs to medium supplemented with human serum restored the expression of CD105. The tri-lineage differentiation of DPSCs cultured under XSF and FBS conditions was similar. We showed that despite reduced CD105 expression levels, DPSCs expanded in XSF medium maintained a functional MSC phenotype. Furthermore, restoration of CD105 expression is likely to occur upon in vivo transplantation, when cells are exposed to human serum.
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Affiliation(s)
- Chengjuan Qu
- Department of Integrative Medical Biology, Umeå University, 901 87, Umeå, Sweden
| | - Maria Brohlin
- Department of Clinical Microbiology, Infection and Immunology, Umeå University, 901 87, Umeå, Sweden.,Division of Clinical Immunology and Transfusion Medicine, Tissue Establishment, Cell Therapy Unit, Department of Laboratory Medicine, Umeå University Hospital, Daniel Naezéns väg, 907 37, Umeå, Sweden
| | - Paul J Kingham
- Department of Integrative Medical Biology, Umeå University, 901 87, Umeå, Sweden
| | - Peyman Kelk
- Department of Integrative Medical Biology, Umeå University, 901 87, Umeå, Sweden.
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