Human Schwann cells exhibit long‐term cell survival,are not tumorigenic and promote repair when transplanted into the contused spinal cord |
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| Authors: | Johana Bastidas Gagani Athauda Gabriela De La Cruz Wai‐Man Chan Roozbeh Golshani Yerko Berrocal Martha Henao Anil Lalwani Chikato Mannoji Mazen Assi P. Anthony Otero Aisha Khan Alexander E. Marcillo Michael Norenberg Allan D. Levi Patrick M. Wood James D. Guest W. Dalton Dietrich Mary Bartlett Bunge Damien D. Pearse |
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| Affiliation: | 1. The Miami Project to Cure Paralysis, The Department of Neurological Surgery, The University of Miami Miller School of Medicine, Miami, Florida;2. The Department of Cellular Biology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida;3. The Department of Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida;4. Translational Pathology Laboratory, Lineberger Comprehensive Cancer Center, Department of Pathology, University of North Carolina School of Medicine, Chapel Hill, North Carolina;5. The Department of Orthopedic Surgery, Chiba University School of Medicine, Chiba, Japan;6. The Department of Pathology, The University of Miami Miller School of Medicine, Miami, Florida;7. The Department of Neurological Surgery, The University of Miami Miller School of Medicine, Miami, Florida;8. The Department of Neurology, The University of Miami Miller School of Medicine, Miami, Florida;9. The Neuroscience Program, The University of Miami Miller School of Medicine, Miami, Florida;10. The Interdisciplinary Stem Cell Institute, The University of Miami Miller School of Medicine, Miami, Florida;11. The Department of Cell Biology, The University of Miami Miller School of Medicine, Miami, Florida;12. Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, Florida |
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| Abstract: | The transplantation of rodent Schwann cells (SCs) provides anatomical and functional restitution in a variety of spinal cord injury (SCI) models, supporting the recent translation of SCs to phase 1 clinical trials for human SCI. Whereas human (Hu)SCs have been examined experimentally in a complete SCI transection paradigm, to date the reported behavior of SCs when transplanted after a clinically relevant contusive SCI has been restricted to the use of rodent SCs. Here, in a xenotransplant, contusive SCI paradigm, the survival, biodistribution, proliferation and tumorgenicity as well as host responses to HuSCs, cultured according to a protocol analogous to that developed for clinical application, were investigated. HuSCs persisted within the contused nude rat spinal cord through 6 months after transplantation (longest time examined), exhibited low cell proliferation, displayed no evidence of tumorigenicity and showed a restricted biodistribution to the lesion. Neuropathological examination of the CNS revealed no adverse effects of HuSCs. Animals exhibiting higher numbers of surviving HuSCs within the lesion showed greater volumes of preserved white matter and host rat SC and astrocyte ingress as well as axon ingrowth and myelination. These results demonstrate the safety of HuSCs when employed in a clinically relevant experimental SCI paradigm. Further, signs of a potentially positive influence of HuSC transplants on host tissue pathology were observed. These findings show that HuSCs exhibit a favorable toxicity profile for up to 6 months after transplantation into the contused rat spinal cord, an important outcome for FDA consideration of their use in human clinical trials. |
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| Keywords: | axon growth gliosis inflammation myelination safety spinal cord injury toxicity xenotransplant |
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