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Angeli LRADE, Santos GBD, Ferreira JRM, Serafim BLC, Lima TZ, Lima LGCADE, Bueno DF, Guarniero R. LOCAL INJECTION OF HUMAN DENTAL PULP STEM CELLS FOR TREATMENT OF JUVENILE AVASCULAR NECROSIS OF THE FEMORAL HEAD: PRELIMINARY RESULTS IN IMMATURE PIGS. ACTA ORTOPEDICA BRASILEIRA 2025; 33:e283445. [PMID: 40206451 PMCID: PMC11978309 DOI: 10.1590/1413-785220243201e283445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Accepted: 04/23/2024] [Indexed: 04/11/2025]
Abstract
Introduction Legg-Calvé-Perthes disease is a major cause of hip joint deformities in children. Currently, experimental research is directed at investigating biological therapies, including the use of human dental pulp stem cells (hDPSC), which have not yet been studied for this purpose in swine models. This study aimed to evaluate whether local injection of hDPSC induces bone mineralization in the proximal femoral epiphysis in an experimental model of avascular necrosis of the femoral head in immature pigs. Methods Ten immature pigs underwent surgery to induce osteonecrosis of the proximal femoral epiphysis on the right side. In the intervention group (IG), hDPSC injections were performed immediately after osteonecrosis induction, and in the control group (CG), no additional procedure was performed. Left hips were used as controls. After 8 weeks, all animals were euthanized, and macroscopic, radiographic, and histological evaluations were performed. Results Bone mineralization was greater in the right hips of the IG compared to the CG (p = 0.0356), with an average mineralization index increase of 77.78% after hDPSC injection. Radiographic evaluation of the epiphyseal index showed a greater collapse in the right IG hips compared to the right CG hips (p < 0.001) and macroscopic evaluation showed a higher chance of the femoral head being flat (p = 0,049). Conclusion The injection of hDPSC into the proximal femoral epiphysis with induced osteonecrosis increases bone mineralization in immature pigs, but these treated hips show more deformity compared to the untreated hips. Level of Evidence IV, Case Series .
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Affiliation(s)
- Luiz Renato Agrizzi DE Angeli
- Universidade de Sao Paulo, Faculdade de Medicina, Hospital das Clinicas HC-FMUSP, Departamento de Ortopedia e Traumatologia DOT, Sao Paulo, SP, Brazil
| | - Gustavo Bispo Dos Santos
- Universidade de Sao Paulo, Faculdade de Medicina, Hospital das Clinicas HC-FMUSP, Departamento de Ortopedia e Traumatologia DOT, Sao Paulo, SP, Brazil
| | | | - Bárbara Lívia Corrêa Serafim
- Universidade de Sao Paulo, Faculdade de Medicina, Hospital das Clinicas HC-FMUSP, Departamento de Ortopedia e Traumatologia DOT, Sao Paulo, SP, Brazil
| | | | | | | | - Roberto Guarniero
- Universidade de Sao Paulo, Faculdade de Medicina, Hospital das Clinicas HC-FMUSP, Departamento de Ortopedia e Traumatologia DOT, Sao Paulo, SP, Brazil
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Fernandes TL, Santanna JPC, de Faria RR, Pastore ER, Bueno DF, Hernandez AJ. Tissue Engineering Construct for Articular Cartilage Restoration with Stromal Cells from Synovium vs. Dental Pulp-A Pre-Clinical Study. Pharmaceutics 2024; 16:1558. [PMID: 39771537 PMCID: PMC11677368 DOI: 10.3390/pharmaceutics16121558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 11/12/2024] [Accepted: 11/25/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND/OBJECTIVES Cartilage injuries and osteoarthritis are prevalent public health problems, due to their disabling nature and economic impact. Mesenchymal stromal cells (MSCs) isolated from different tissues have the immunomodulatory capacity to regulate local joint environment. This translational study aims to compare cartilage restoration from MSCs from the synovial membrane (SM) and dental pulp (DP) by a tissue-engineered construct with Good Manufacturing Practices. METHODS A controlled experimental study was conducted on fourteen miniature pigs, using scaffold-free Tissue Engineering Constructs (TECs) from DP and SM MSCs, with a 6-month follow-up. Total thickness cartilage defects were created in both hind knees; one side was left untreated and the other received a TEC from either DP (n = 7) or SM (n = 7). An MRI assessed the morphology using the MOCART scoring system, T2 mapping evaluated water, and collagen fiber composition, and histological analysis was performed using the ICRS-2 score. RESULTS The untreated group had a mean MOCART value of 46.2 ± 13.4, while the SM-treated group was 65.7 ± 15.5 (p < 0.05) and the DP-treated group was 59.0 ± 7.9 (n.s.). The T2 mapping indicated a mean value of T2 of 54.9 ± 1.9 for native cartilage, with the untreated group at 50.9 ± 2.4 (p < 0.05). No difference was found between the T2 value of native cartilage and the treated groups. The ICRS-2 mean values were 42.1 ± 14.8 for the untreated group, 64.3 ± 19.0 for SM (p < 0.05), and 54.3 ± 12.2 for DP (n.s.). CONCLUSION MRI and histological analysis indicated that TEC treatment led to superior cartilage coverage and quality compared to the defect group. TECs from SM demonstrated better results than the defect group in the histological assessment.
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Affiliation(s)
- Tiago Lazzaretti Fernandes
- Sports Medicine Division, Institute of Orthopedics and Traumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05403-010, SP, Brazil; (J.P.C.S.); (R.R.d.F.); (E.R.P.); (A.J.H.)
- Hospital Sírio-Libanês, São Paulo 05403-010, SP, Brazil
| | - João Paulo Cortez Santanna
- Sports Medicine Division, Institute of Orthopedics and Traumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05403-010, SP, Brazil; (J.P.C.S.); (R.R.d.F.); (E.R.P.); (A.J.H.)
| | - Rafaella Rogatto de Faria
- Sports Medicine Division, Institute of Orthopedics and Traumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05403-010, SP, Brazil; (J.P.C.S.); (R.R.d.F.); (E.R.P.); (A.J.H.)
| | - Enzo Radaic Pastore
- Sports Medicine Division, Institute of Orthopedics and Traumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05403-010, SP, Brazil; (J.P.C.S.); (R.R.d.F.); (E.R.P.); (A.J.H.)
| | - Daniela Franco Bueno
- Faculdade Israelita de Ciências da Saúde Albert Einstein, São Paulo 05403-010, SP, Brazil;
| | - Arnaldo José Hernandez
- Sports Medicine Division, Institute of Orthopedics and Traumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05403-010, SP, Brazil; (J.P.C.S.); (R.R.d.F.); (E.R.P.); (A.J.H.)
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dos Santos NCC, Cotrim KC, Achôa GL, Kalil EC, Kantarci A, Bueno DF. The Use of Mesenchymal Stromal/Stem Cells (MSC) for Periodontal and Peri-implant Regeneration: Scoping Review. Braz Dent J 2024; 35:e246134. [PMID: 39476117 PMCID: PMC11506238 DOI: 10.1590/0103-6440202406134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 06/06/2024] [Indexed: 11/03/2024] Open
Abstract
The necessity for regenerating peri-implant and periodontal tissues is increasingly apparent. Periodontal diseases can result in a significant loss of clinical attachment level, and tissue regeneration stands as the ultimate goal of periodontal therapy. With the rise of osseointegration, the prosthetic rehabilitation of missing teeth using dental implants has surged, leading to a frequent need for alveolar bone regeneration around implants. This review assessed studies reporting various sources of mesenchymal stromal/stem cells (MSC) and their potential in regenerating periodontal and peri-implant bone tissue. A search was conducted across seven databases spanning the past decade. Three authors independently screened all identified titles and abstracts for eligibility, generating tables to summarize included studies in animals and humans separately. A total of 55 articles were chosen for final evaluation, showcasing five origins of MSC used in humans and animals for regenerating periodontal tissues and peri-implant bone, using different types of scaffolds. Overall, research from the past decades supports the effectiveness of MSC in promoting periodontal and peri-implant regeneration. However, the impact of MSC on regenerative therapies in humans is still in its initial stages. Future research should optimize MSC application protocols by combining techniques, such as the use of nanomedicine and 3D printing for tissue engineering. Clinical studies should also understand the long-term effects and compare MSC therapies with current treatment modalities. By addressing these areas, the scientific community can ensure that MSC therapies are both safe and effective, ultimately enhancing therapeutic strategies and treatment outcomes in Periodontology and Implantology.
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Affiliation(s)
- Nidia C Castro dos Santos
- Dental Research Division, Guarulhos University, Guarulhos, SP, Brazil
- School of Dental Medicine, Albert Einstein Israelite Hospital, São Paulo, SP, Brazil
- The ADA Forsyth Institute, Cambridge, MA, United States
| | - Khalila C Cotrim
- Dental Research Division, Guarulhos University, Guarulhos, SP, Brazil
| | - Gustavo L Achôa
- Núcleo de Pesquisa e Reabilitação de Lesões Lábio Palatais Prefeito Luiz Gomes, Oral and Maxillofacial Surgery Department, Joinville, SC, Brazil
| | - Eduardo C Kalil
- Dental Research Division, Guarulhos University, Guarulhos, SP, Brazil
| | - Alpdogan Kantarci
- The ADA Forsyth Institute, Cambridge, MA, United States
- School of Dental Medicine, Harvard University, Boston, MA, United States
| | - Daniela F Bueno
- School of Dental Medicine, Albert Einstein Israelite Hospital, São Paulo, SP, Brazil
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Sun X, Lin Z, Xu N, Chen Y, Bian S, Zheng W. Identifying Dental Pulp Stem Cell as a Novel Therapeutic trategy for Digestive Diseases. Curr Stem Cell Res Ther 2024; 19:1293-1302. [PMID: 38018204 DOI: 10.2174/011574888x275737231120045815] [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: 08/04/2023] [Revised: 10/09/2023] [Accepted: 10/13/2023] [Indexed: 11/30/2023]
Abstract
Mesenchymal stem cells (MSCs) have been identified as potential therapeutics for various diseases. In contrast to other sources of MSCs, dental stem cells (DSCs) have received increased attention due to their high activity and easy accessibility. Among them, dental pulp stem cells (DPSCs) exhibit superior self-renewal, multipotency, immunomodulatory, and regenerative capacities. Following their inspiring performance in animal models and clinical trials, DPSCs show pharmacological potential in regenerative medicine. In this review, we have generalized the sources, heterogeneity, and biological characteristics of DPSCs, as well as compared them with other types of dental stem cells. In addition, we summarized the application of DPSCs in digestive diseases (such as liver, esophageal, and intestinal diseases), highlighting their regenerative and pharmacological potential based on the existing preclinical and clinical evidence. Specifically, DPSCs can be home to injured or inflamed tissues and exert repair and regeneration functions by facilitating immune regulation, anti-inflammation, and directional differentiation. Although DPSCs have a rosy prospect, future studies should handle the underlying drawbacks and pave the way for the identification of DPSCs as novel regenerative medicine.
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Affiliation(s)
- Xieyin Sun
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China
| | - Zhaoyi Lin
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China
| | - Nuo Xu
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China
| | - Yinqi Chen
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China
| | - Saiyan Bian
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China
| | - Wenjie Zheng
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China
- Research Institute of Stem Cells, Center of Clinical Trials, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China
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Song WP, Jin LY, Zhu MD, Wang H, Xia DS. Clinical trials using dental stem cells: 2022 update. World J Stem Cells 2023; 15:31-51. [PMID: 37007456 PMCID: PMC10052340 DOI: 10.4252/wjsc.v15.i3.31] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/20/2023] [Accepted: 03/08/2023] [Indexed: 03/23/2023] Open
Abstract
For nearly 20 years, dental stem cells (DSCs) have been successfully isolated from mature/immature teeth and surrounding tissue, including dental pulp of permanent teeth and exfoliated deciduous teeth, periodontal ligaments, dental follicles, and gingival and apical papilla. They have several properties (such as self-renewal, multidirectional differentiation, and immunomodulation) and exhibit enormous potential for clinical applications. To date, many clinical articles and clinical trials using DSCs have reported the treatment of pulpitis, periapical lesions, periodontitis, cleft lip and palate, acute ischemic stroke, and so on, and DSC-based therapies obtained satisfactory effects in most clinical trials. In these studies, no adverse events were reported, which suggested the safety of DSC-based therapy. In this review, we outline the characteristics of DSCs and summarize clinical trials and their safety as DSC-based therapies. Meanwhile, we also present the current limitations and perspectives of DSC-based therapy (such as harvesting DSCs from inflamed tissue, applying DSC-conditioned medium/DSC-derived extracellular vesicles, and expanding-free strategies) to provide a theoretical basis for their clinical applications.
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Affiliation(s)
- Wen-Peng Song
- Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Lu-Yuan Jin
- Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China
| | - Meng-Di Zhu
- Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China
| | - Hao Wang
- Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Deng-Sheng Xia
- Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China.
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Alfayez E, Alghamdi F. Clinical Application of Stem Cell Therapy in Reconstructing Maxillary Cleft Alveolar Bone Defects: A Systematic Review of Randomized Clinical Trials. Cureus 2022; 14:e23111. [PMID: 35425680 PMCID: PMC9002340 DOI: 10.7759/cureus.23111] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/12/2022] [Indexed: 11/25/2022] Open
Abstract
An alveolar cleft is the most common congenital bone defect. This systematic review aimed to investigate the use of stem cells for alveolar cleft repair and summarize the outcomes of clinical research studies. The electronic databases PubMed, Scopus, Web of Sciences, and Google Scholar were utilized to search the literature for relevant studies after administering specific inclusion and exclusion criteria. The search included articles that were published from 2011 to 2021 and specific keywords were used in the databases. The search was completed by two independent reviewers following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.Only four studies satisfied both the inclusion and exclusion criteria and were included in this systematic review. These studies investigated different aspects of bone reconstruction in the maxillary alveolar bone by stem cells, including cell types, clinical applications, biomaterial scaffolds, and follow-up period. The accumulated evidence in this systematic review is limited and insufficient to support the role of stem cell use in bone regeneration of maxillary alveolar bone defects. The outcome of using stem cells was studied only in 57 subjects from the four included studies. Although the noninvasive methods of isolating stem cells make them attractive resources for bone regeneration, more research is required in order to standardize and investigate stem cell therapy. This should be done beforehand in adults in less invasive procedures such as bone defect repair in dentistry prior to considering this type of therapy in this vulnerable patient population.
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Affiliation(s)
- Eman Alfayez
- Oral Biology, Faculty of Dentistry, King Abdulaziz University, Jeddah, SAU
| | - Faisal Alghamdi
- Oral Biology, Faculty of Dentistry, King Abdulaziz University, Jeddah, SAU
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SantAnna JPC, Faria RR, Assad IP, Pinheiro CCG, Aiello VD, Albuquerque-Neto C, Bortolussi R, Cestari IA, Maizato MJS, Hernandez AJ, Bueno DF, Fernandes TL. Tissue Engineering and Cell Therapy for Cartilage Repair: Preclinical Evaluation Methods. Tissue Eng Part C Methods 2022; 28:73-82. [PMID: 35107353 DOI: 10.1089/ten.tec.2021.0208] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Abstract
A chondral injury is a limiting disease that can affect the quality of life and be an economic burden due to the cost of immediate treatment and loss in work productivity. If left untreated, such an injury may progress to osteoarthritis, a degenerative and debilitating joint disease characterized by pain and functional impairment. Mesenchymal stromal cells (MSCs), which have immune-modulatory properties and the ability to differentiate into chondroblasts and osteoblasts, are a predictable source for the treatment of cartilage injuries. This article presents tools to evaluate cartilage restoration by tissue engineering and cell therapy treatment in a translational and preclinical large animal model. In this controlled experimental study with 14 miniature pigs, a scaffold-free tissue engineering construct (TEC) derived from dental pulp and synovial MSCs for cartilage therapy was tested. Total thickness cartilage defects were performed in both posterior knees. The defect was left empty in one of the knees, and the other received the TEC. The tissue repair was morphologically assessed by magnetic resonance imaging (MRI) using the three-dimensional double echo steady-state (3D-DESS) sequence, and compositional assessment was carried out based on the T2 mapping technique. The osteochondral specimens were fixed for histopathology, decalcified, subjected to standard histological processing, sectioned, and stained with hematoxylin and eosin. The sections stained for immunohistochemical detection of collagen types were digested with pepsin and chondroitinase and incubated with antibodies against them. The mechanical evaluation involved analysis of Young's modulus of the cartilage samples based on the indentation and maximum compression test. In addition, a finite element model was used to simulate and characterize properties of the osteochondral block. At 6 months after surgery, there were no complications with the animals and the MRI, histological, immunohistochemical, and biomechanical evaluations proved to be effective and qualified to differentiate good quality chondral repair from inadequate repair tissue. The proposed methods were feasible and capable to properly evaluate the defect filled with TEC containing stromal cells after 6 months of follow-up in a large animal model for articular cartilage restoration. Impact Statement Articular chondral injuries are prevalent and represent an economic burden due to the cost of treatment. The engineering of cartilage tissue can promote the repair of chondral injuries and is dependent on selecting appropriate cells and biocompatible frameworks. In this article, methods for evaluation of a scaffold-free cell delivery system made from mesenchymal stromal cells were present in a translational study that allows further clinical safety and efficacy trials.
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Affiliation(s)
- João P C SantAnna
- Grupo de Medicina do Esporte, Instituto de Ortopedia e Traumatologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Rafaella R Faria
- Instituto de Ortopedia e Traumatologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Isabella P Assad
- Instituto de Ortopedia e Traumatologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | - Vera D Aiello
- Laboratório de Patologia, Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil
| | - Cyro Albuquerque-Neto
- Department of Mechanical Engineering, Centro Universitário da FEI, São Paulo, Brazil
| | - Roberto Bortolussi
- Department of Mechanical Engineering, Centro Universitário da FEI, São Paulo, Brazil
| | - Idágene A Cestari
- Laboratório de Investigação Médica em Bioengenharia, Instituto do Coração, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Marina J S Maizato
- Laboratório de Investigação Médica em Bioengenharia, Instituto do Coração, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Arnaldo J Hernandez
- Grupo de Medicina do Esporte, Instituto de Ortopedia e Traumatologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | - Tiago L Fernandes
- Grupo de Medicina do Esporte, Instituto de Ortopedia e Traumatologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
- Hospital Sírio-Libanês, São Paulo, Brazil
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Bueno DF, Kabayashi GS, Pinheiro CCG, Tanikawa DYS, Raposo-Amaral CE, Rocha DL, Ferreira JRM, Shibuya Y, Hokugo A, Jarrahy R, ZuK PA, Passos-Bueno MR. Human levator veli palatini muscle: a novel source of mesenchymal stromal cells for use in the rehabilitation of patients with congenital craniofacial malformations. Stem Cell Res Ther 2020; 11:501. [PMID: 33239080 PMCID: PMC7687766 DOI: 10.1186/s13287-020-02017-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 11/04/2020] [Indexed: 12/02/2022] Open
Abstract
Background Bone reconstruction in congenital craniofacial differences, which affect about 2–3% of newborns, has long been the focus of intensive research in the field of bone tissue engineering. The possibility of using mesenchymal stromal cells in regenerative medicine protocols has opened a new field of investigation aimed at finding optimal sources of multipotent cells that can be isolated via non-invasive procedures. In this study, we analyzed whether levator veli palatini muscle fragments, which can be readily obtained in non-invasive manner during palatoplasty in cleft palate patients, represent a novel source of MSCs with osteogenic potential. Methods We obtained levator veli palatini muscle fragments (3–5 mm3), during surgical repair of cleft palate in 5 unrelated patients. Mesenchymal stromal cells were isolated from the muscle using a pre-plating technique and other standard practices. The multipotent nature of the isolated stromal cells was demonstrated via flow cytometry analysis and by induction along osteogenic, adipogenic, and chondrogenic differentiation pathways. To demonstrate the osteogenic potential of these cells in vivo, they were used to reconstruct a critical-sized full-thickness calvarial defect model in immunocompetent rats. Results Flow cytometry analysis showed that the isolated stromal cells were positive for mesenchymal stem cell antigens (CD29, CD44, CD73, CD90, and CD105) and negative for hematopoietic (CD34 and CD45) or endothelial cell markers (CD31). The cells successfully underwent osteogenic, chondrogenic, and adipogenic cell differentiation under appropriate cell culture conditions. Calvarial defects treated with CellCeram™ scaffolds seeded with the isolated levator veli palatini muscle cells showed greater bone healing compared to defects treated with acellular scaffolds. Conclusion Cells derived from levator veli palatini muscle have phenotypic characteristics similar to other mesenchymal stromal cells, both in vitro and in vivo. Our findings suggest that these cells may have clinical relevance in the surgical rehabilitation of patients with cleft palate and other craniofacial anomalies characterized by significant bone deficit. Supplementary information The online version contains supplementary material available at 10.1186/s13287-020-02017-7.
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Affiliation(s)
- Daniela Franco Bueno
- Hospital Sírio-Libanês, Instituto de Ensino e Pesquisa, São Paulo, SP, Brazil. .,Hospital Municipal Infantil Menino Jesus, São Paulo, SP, Brazil.
| | - Gerson Shigueru Kabayashi
- Universidade de São Paulo - USP, Instituto de Biociências, Centro de Pesquisa sobre o Genoma Humano e Células-Tronco, São Paulo, SP, Brazil
| | | | - Daniela Y S Tanikawa
- Hospital Sírio-Libanês, Instituto de Ensino e Pesquisa, São Paulo, SP, Brazil.,Hospital Municipal Infantil Menino Jesus, São Paulo, SP, Brazil
| | | | | | - José Ricardo Muniz Ferreira
- Instituto Militar de Engenharia (IME), Departamento de Ciências de Materiais, Programa de Pós-graduação em Ciências de Materiais, Rio de Janeiro, RJ, Brazil
| | - Yoichiro Shibuya
- Division of Plastic and Reconstructive Surgery, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA
| | - Akishige Hokugo
- Division of Plastic and Reconstructive Surgery, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA
| | - Reza Jarrahy
- Division of Plastic and Reconstructive Surgery, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA
| | - Patricia A ZuK
- Division of Plastic and Reconstructive Surgery, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA
| | - Maria Rita Passos-Bueno
- Universidade de São Paulo - USP, Instituto de Biociências, Centro de Pesquisa sobre o Genoma Humano e Células-Tronco, São Paulo, SP, Brazil
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Najar M, Martel-Pelletier J, Pelletier JP, Fahmi H. Mesenchymal Stromal Cell Immunology for Efficient and Safe Treatment of Osteoarthritis. Front Cell Dev Biol 2020; 8:567813. [PMID: 33072752 PMCID: PMC7536322 DOI: 10.3389/fcell.2020.567813] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Accepted: 08/24/2020] [Indexed: 12/11/2022] Open
Abstract
Mesenchymal stem cell (MSC) therapy represents a promising approach for the treatment of osteoarthritis (OA). MSCs can be readily isolated from multiple sources and expanded ex vivo for possible clinical application. They possess a unique immunological profile and regulatory machinery that underline their therapeutic effects. They also have the capacity to sense the changes within the tissue environment to display the adequate response. Indeed, there is a close interaction between MSCs and the host cells. Accordingly, MSCs demonstrate encouraging results for a variety of diseases including OA. However, their effectiveness needs to be improved. In this review, we selected to discuss the importance of the immunological features of MSCs, including the type of transplantation and the immune and blood compatibility. It is important to consider MSC immune evasive rather than immune privileged. We also highlighted some of the actions/mechanisms that are displayed during tissue healing including the response of MSCs to injury signals, their interaction with the immune system, and the impact of their lifespan. Finally, we briefly summarized the results of clinical studies reporting on the application of MSCs for the treatment of OA. The research field of MSCs is inspiring and innovative but requires more knowledge about the immunobiological properties of these cells. A better understanding of these features will be key for developing a safe and efficient medicinal product for clinical use in OA.
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Affiliation(s)
- Mehdi Najar
- Osteoarthritis Research Unit, University of Montreal Hospital Research Center, Department of Medicine, University of Montreal, Montreal, QC, Canada
| | - Johanne Martel-Pelletier
- Osteoarthritis Research Unit, University of Montreal Hospital Research Center, Department of Medicine, University of Montreal, Montreal, QC, Canada
| | - Jean-Pierre Pelletier
- Osteoarthritis Research Unit, University of Montreal Hospital Research Center, Department of Medicine, University of Montreal, Montreal, QC, Canada
| | - Hassan Fahmi
- Osteoarthritis Research Unit, University of Montreal Hospital Research Center, Department of Medicine, University of Montreal, Montreal, QC, Canada
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