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Transplantation of human glial-restricted neural precursors into injured spinal cord promotes functional and sensory recovery without causing allodynia
Authors:Arshak R Alexanian  Clive N Svendsen  Maria J Crowe  Shekar N Kurpad
Institution:Neuroscience Research Laboratories, Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA;Anatomy and Neurology, Waisman Center, University of Wisconsin–Madison, Madison, Wisconsin, USA;Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA;Max-Delbrück-Center for Molecular Medicine, Berlin-Buch, Germany;Stem Cell Lab, National Center for Cell Science, Ganeshkhind, Pune, India;Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA;Department of Hematology, Xinqiao Hospital;Department of Chemical Defense and Toxicology, Third Military Medical University, Chongqing, China;Department of Neurology, First Affiliated Hospital;Stem Cells and Tissue Engineering Research Center, Sun Yat-Sen University, Guangzhou, China;Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea;Department of Surgery, Ulsan University College of Medicine and Asan Medical Center, Seoul, Republic of Korea
Abstract:Background aimsTraumatic injuries of the central nervous system cause damage and degeneration of specific cell populations with subsequent functional loss. Cell transplantation is a strategy to treat such injuries by replacing lost or damaged cell populations. Many kinds of cells are considered candidates for intraspinal transplantation. Human neural precursor cells (hNPC) derived from post-mortem fetal tissue are easy to isolate and expand, and are capable of producing large numbers of neuronal and glial cells. After transplantation into the nervous system, hNPC produce mature neural phenotypes and permit functional improvement in some models of neurodegenerative disease. In this study, we aimed to elucidate the therapeutic effect of different neuronal and glial progenitor populations of hNPC on locomotor and sensory functions of spinal cord-injured (SCI) ratsMethodsDifferent populations of progenitor cells were obtained from hNPC by cell sorting and neural induction, resulting in cell cultures that were NCAM+ A2B5+, NCAM+ A2B5? or A2B5+ NG2+. These different cell populations were then tested for efficacy in repair of the injured spinal cord by transplantation into rats with SCIResultsThe A2B5+ NG2+ population of hNPC significantly improved locomotor and sensory (hindlimb) functional recovery of SCI rats. Importantly, no abnormal pain responses were observed in the forelimbs following transplantationConclusionsThis treatment approach can improve functional recovery after SCI without causing allodynia. Further studies will be conducted to investigate the ability of A2B5+ NG2+ cells to survive, differentiate and integrate in the injured spinal cord.
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