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Cell therapy for spinal cord repair: optimization of biologic scaffolds for survival and neural differentiation of human bone marrow stromal cells
Authors:Mercedes Zurita  Laura Otero  Concepción Aguayo  Celia Bonilla  Edgar Ferreira  Avelino Parajón  Jesús Vaquero
Institution:1. Department of Surgery, St. Jude Children''s Research Hospital, Memphis, TN;2. Department of Surgery, University of Tennessee Health Science Center, Memphis, TN;3. Department of Diagnostic Imaging, St. Jude Children''s Research Hospital, Memphis, TN;4. Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN;5. Department of Biostatistics, St. Jude Children''s Research Hospital, Memphis, TN;6. Department of Oncology, Children''s National Medical Center, Washington, DC;7. Department of Urology, Seattle Children''s Hospital, Seattle, WA;8. Division of Pediatric Urology, Levine Children''s Hospital, Charlotte, NC;9. Department of Oncology, St. Jude Children''s Research Hospital, Memphis, TN;10. Department of Radiation Oncology, St. Jude Children''s Hospital, Memphis, TN;11. Department of Epidemiology and Cancer Control, St. Jude Children''s Research Hospital, Memphis, TN;1. Yale School of Medicine, New Haven, Connecticut;2. Department of Radiology and Biomedical Imaging, Yale School of Medicine, Box 208042, Tompkins East 2, 333 Cedar St, New Haven, CT 06520-8042;3. Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut;4. Department of Economics, Yale School of Medicine, New Haven, Connecticut;5. Department of Management, Yale School of Medicine, New Haven, Connecticut;6. Department of Public Health, Yale School of Medicine, New Haven, Connecticut;7. Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut;8. Department of Radiology, Northwell Health, Great Neck, New York
Abstract:Background aimsThe suppression of cell apoptosis using a biodegradable scaffold to replace the missing or altered extracellular matrix (ECM) could increase the survival of transplanted cells and thus increase the effectiveness of cell therapy.MethodsWe studied the best conditions for the proliferation and differentiation of human bone marrow stromal cells (hBMSC) when cultured on different biologic scaffolds derived from fibrin and blood plasma, and analyzed the best concentrations of fibrinogen, thrombin and calcium chloride for favoring cell survival. The induction of neural differentiation of hBMSC was done by adding to these scaffolds different growth factors, such as nerve growth factor (NGF), brain-derived-neurotrophic factor (BDNF) and retinoic acid (RA), at concentrations of 100 ng/mL (NGF and BDNF) and 1 μ/mL (RA), over 7 days.ResultsAlthough both types of scaffold allowed survival and neural differentiation of hBMSC, the results showed a clear superiority of platelet-rich plasma (PRP) scaffolds, mainly after BDNF administration, allowing most of the hBMSC to survive and differentiate into a neural phenotype.ConclusionsGiven that clinical trials for spinal cord injury using hBMSC are starting, these findings may have important clinical applications.
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