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Human induced pluripotent stem cells integrate, create synapses and extend long axons after spinal cord injury
Numerous interventions have been explored in animal models using cells differentiated from human induced pluripotent stem cells (iPSCs) in the context of neural injury with some success. Our work seeks to transplant cells that are generated from hiPSCs into regionally specific spinal neural progenit...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980929/ https://www.ncbi.nlm.nih.gov/pubmed/35257489 http://dx.doi.org/10.1111/jcmm.17217 |
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author | Lavoie, Nicolas Stoflet Truong, Vincent Malone, Dane Pengo, Thomas Patil, Nandadevi Dutton, James R. Parr, Ann M. |
author_facet | Lavoie, Nicolas Stoflet Truong, Vincent Malone, Dane Pengo, Thomas Patil, Nandadevi Dutton, James R. Parr, Ann M. |
author_sort | Lavoie, Nicolas Stoflet |
collection | PubMed |
description | Numerous interventions have been explored in animal models using cells differentiated from human induced pluripotent stem cells (iPSCs) in the context of neural injury with some success. Our work seeks to transplant cells that are generated from hiPSCs into regionally specific spinal neural progenitor cells (sNPCs) utilizing a novel accelerated differentiation protocol designed for clinical translation. We chose a xenotransplantation model because our laboratory is focused on the behaviour of human cells in order to bring this potential therapy to translation. Cells were transplanted into adult immunodeficient rats after moderate contusion spinal cord injury (SCI). Twelve weeks later, cells derived from the transplanted sNPCs survived and differentiated into neurons and glia that filled the lesion cavity and produced a thoracic spinal cord transcriptional program in vivo. Furthermore, neurogenesis and ionic channel expression were promoted within the adjacent host spinal cord tissue. Transplanted cells displayed robust integration properties including synapse formation and myelination by host oligodendrocytes. Axons from transplanted hiPSC sNPC‐derived cells extended both rostrally and caudally from the SCI transplant site, rostrally approximately 6 cm into supraspinal structures. Thus, iPSC‐derived sNPCs may provide a patient‐specific cell source for patients with SCI that could provide a relay system across the site of injury. |
format | Online Article Text |
id | pubmed-8980929 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89809292022-04-11 Human induced pluripotent stem cells integrate, create synapses and extend long axons after spinal cord injury Lavoie, Nicolas Stoflet Truong, Vincent Malone, Dane Pengo, Thomas Patil, Nandadevi Dutton, James R. Parr, Ann M. J Cell Mol Med Original Articles Numerous interventions have been explored in animal models using cells differentiated from human induced pluripotent stem cells (iPSCs) in the context of neural injury with some success. Our work seeks to transplant cells that are generated from hiPSCs into regionally specific spinal neural progenitor cells (sNPCs) utilizing a novel accelerated differentiation protocol designed for clinical translation. We chose a xenotransplantation model because our laboratory is focused on the behaviour of human cells in order to bring this potential therapy to translation. Cells were transplanted into adult immunodeficient rats after moderate contusion spinal cord injury (SCI). Twelve weeks later, cells derived from the transplanted sNPCs survived and differentiated into neurons and glia that filled the lesion cavity and produced a thoracic spinal cord transcriptional program in vivo. Furthermore, neurogenesis and ionic channel expression were promoted within the adjacent host spinal cord tissue. Transplanted cells displayed robust integration properties including synapse formation and myelination by host oligodendrocytes. Axons from transplanted hiPSC sNPC‐derived cells extended both rostrally and caudally from the SCI transplant site, rostrally approximately 6 cm into supraspinal structures. Thus, iPSC‐derived sNPCs may provide a patient‐specific cell source for patients with SCI that could provide a relay system across the site of injury. John Wiley and Sons Inc. 2022-03-08 2022-04 /pmc/articles/PMC8980929/ /pubmed/35257489 http://dx.doi.org/10.1111/jcmm.17217 Text en © 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Lavoie, Nicolas Stoflet Truong, Vincent Malone, Dane Pengo, Thomas Patil, Nandadevi Dutton, James R. Parr, Ann M. Human induced pluripotent stem cells integrate, create synapses and extend long axons after spinal cord injury |
title | Human induced pluripotent stem cells integrate, create synapses and extend long axons after spinal cord injury |
title_full | Human induced pluripotent stem cells integrate, create synapses and extend long axons after spinal cord injury |
title_fullStr | Human induced pluripotent stem cells integrate, create synapses and extend long axons after spinal cord injury |
title_full_unstemmed | Human induced pluripotent stem cells integrate, create synapses and extend long axons after spinal cord injury |
title_short | Human induced pluripotent stem cells integrate, create synapses and extend long axons after spinal cord injury |
title_sort | human induced pluripotent stem cells integrate, create synapses and extend long axons after spinal cord injury |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980929/ https://www.ncbi.nlm.nih.gov/pubmed/35257489 http://dx.doi.org/10.1111/jcmm.17217 |
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