Human gingival mesenchymal stem cells improve movement disorders and tyrosine hydroxylase neuronal damage in Parkinson disease rats |
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| Affiliation: | 1. School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China;2. Daxing Research Institute, University of Science and Technology Beijing, Beijing, China;3. Cell Therapy Laboratory, First Hospital of Hebei Medical University, Shijiazhuang, China;4. Department of Immunology, Basic Medical College, Hebei Medical University, Shijiazhuang, China;1. Department of Regenerative Medicine Research, Texas Heart Institute, Houston, Texas, USA;2. Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA;3. Department of Chemistry, Rice University, Houston, Texas, USA;4. Chemistry–Biology Interface Predoctoral Training Program, Stanford University, Stanford, California, USA;5. Department of Molecular and Human Genetics, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute, Texas Children''s Hospital, Houston, Texas, USA;6. Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children''s Hospital, Houston, Texas, USA;7. Department of Pathology and Laboratory Medicine, McGovern Medical School, University of Texas Health Science Center, Houston, Texas, USA;8. Center for Clinical Research, Texas Heart Institute, Houston, Texas, USA;1. Daxing Research Institute, University of Science and Technology Beijing, Beijing, China;2. School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China;1. Graduate Program for Collective Health, Faculty of Health Sciences, University of Brasilia, Brasilia, Brazil;2. Oswaldo Cruz Foundation, Rio de Janeiro, Brazil;3. Departament of Hemotherapy and Cell Therapy, Israelita Albert Einstein Hospital, São Paulo, Brazil;4. Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;5. Postgraduate Program in Health Sciences and Technologies, Faculty of Ceilandia, University of Brasilia, Brasília, Brazil;6. Collective Health School, Faculty of Ceilandia, University of Brasilia, Brasília, Brazil;1. University of Vermont College of Medicine, Burlington, Vermont, USA;2. Department of Immunology, Duke University, Durham, North Carolina, USA;3. Marcus Center for Cellular Cures, Duke University, Durham, North Carolina, USA;4. Department of Pathology, Duke University, Durham, North Carolina, USA;5. Department of Neurosurgery, Duke University, Durham, North Carolina, USA;6. Department of Medicine, University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA;7. IMPACT-Center for Interventional Medicine for precision and advanced cellular therapy, Universidad de los Andes, Santiago, Chile;8. Cells for Cells and Consorcio Regenero, Chilean Consortium for Regenerative Medicine, Santiago, Chile;9. Department of Medicine, Section of Hematology, University of Verona, Verona, Italy;10. Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada;11. Anesthesiology and Pain Medicine, University of Ottawa, Ottawa, Ontario, Canada;12. Clinical Epidemiology, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada;13. Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada;14. Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden;15. Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden;16. Department of Internal Medicine, Stem Cell Program and Institute for Regenerative Cures, University of California Davis, Sacramento, California, USA;17. UF Scripps Biomedical Research, Jupiter, Florida, USA;18. Laboratory of Pulmonary Investigation, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;19. The First Affiliated Hospital, Soochow University Institutes for Translational Medicine, Suzhou, China;20. Institute of Health Sciences, Chinese Academy of Sciences, Shanghai, China;21. UMR U1236-MICMAC, Immunology and Cell Therapy Lab, Rennes University Hospital, Rennes, France;22. Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute, University Health Network, Toronto, Canada;23. Krembil Research Institute, University Health Network, Toronto, Canada;24. Institute of Biomedical Engineering, University of Toronto, Toronto, Canada;25. Department of Medicine, Division of Hematology, University of Toronto, Toronto, Canada;26. Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland |
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| Abstract: | Background aimsGingival mesenchymal stem cells (GMSCs) demonstrate high proliferation, trilineage differentiation and immunomodulatory properties. Parkinson disease (PD) is the second most common type of neurodegenerative disease. This study aimed to explore the effect and mechanism of GMSC-based therapy in 6-hydroxydopamine-induced PD rats.MethodsRNA sequencing and quantitative proteomics technology was used to validate the neuroprotective role of GMSCs therapeutic in 6-Hydroxydopamine -induced PD model in vitro and in vivo. Western blotting, immunofluorescence and real-time quantitative PCR verified the molecular mechanism of GMSCs treatment.ResultsIntravenous injection of GMSCs improved rotation and forelimb misalignment behavior, enhanced the anti-apoptotic B-cell lymphoma 2/B-cell lymphoma 2-associated X axis, protected tyrosine hydroxylase neurons, decreased the activation of astrocytes and reduced the astrocyte marker glial fibrillary acidic protein and microglia marker ionized calcium‐binding adaptor molecule 1 in the substantia nigra and striatum of PD rats. The authors found that GMSCs upregulated nerve regeneration-related molecules and inhibited metabolic disorders and the activation of signal transducer and activator of transcription 3. GMSCs showed a strong ability to protect neurons and reduce mitochondrial membrane potential damage and reactive oxygen species accumulation. The safety of GMSC transplantation was confirmed by the lack of tumor formation following subcutaneous transplantation into nude mice for up to 8 weeks.ConclusionsThe authors’ research helps to explain the mechanism of GMSC-based therapeutic strategies and promote potential clinical application in Parkinson disease. |
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