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Cryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo
A major challenge for clinical application of pluripotent stem cell therapy for Parkinson's disease (PD) is large-scale manufacturing and cryopreservation of neurons that can be efficiently prepared with minimal manipulation. To address this obstacle, midbrain dopamine neurons were derived from...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511045/ https://www.ncbi.nlm.nih.gov/pubmed/28579395 http://dx.doi.org/10.1016/j.stemcr.2017.04.033 |
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author | Wakeman, Dustin R. Hiller, Benjamin M. Marmion, David J. McMahon, Christopher W. Corbett, Grant T. Mangan, Kile P. Ma, Junyi Little, Lauren E. Xie, Zhong Perez-Rosello, Tamara Guzman, Jaime N. Surmeier, D. James Kordower, Jeffrey H. |
author_facet | Wakeman, Dustin R. Hiller, Benjamin M. Marmion, David J. McMahon, Christopher W. Corbett, Grant T. Mangan, Kile P. Ma, Junyi Little, Lauren E. Xie, Zhong Perez-Rosello, Tamara Guzman, Jaime N. Surmeier, D. James Kordower, Jeffrey H. |
author_sort | Wakeman, Dustin R. |
collection | PubMed |
description | A major challenge for clinical application of pluripotent stem cell therapy for Parkinson's disease (PD) is large-scale manufacturing and cryopreservation of neurons that can be efficiently prepared with minimal manipulation. To address this obstacle, midbrain dopamine neurons were derived from human induced pluripotent stem cells (iPSC-mDA) and cryopreserved in large production lots for biochemical and transplantation studies. Cryopreserved, post-mitotic iPSC-mDA neurons retained high viability with gene, protein, and electrophysiological signatures consistent with midbrain floor-plate lineage. To test therapeutic efficacy, cryopreserved iPSC-mDA neurons were transplanted without subculturing into the 6-OHDA-lesioned rat and MPTP-lesioned non-human-primate models of PD. Grafted neurons retained midbrain lineage with extensive fiber innervation in both rodents and monkeys. Behavioral assessment in 6-OHDA-lesioned rats demonstrated significant reversal in functional deficits up to 6 months post transplantation with reinnervation of the host striatum and no aberrant growth, supporting the translational development of pluripotent cell-based therapies in PD. |
format | Online Article Text |
id | pubmed-5511045 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-55110452017-07-21 Cryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo Wakeman, Dustin R. Hiller, Benjamin M. Marmion, David J. McMahon, Christopher W. Corbett, Grant T. Mangan, Kile P. Ma, Junyi Little, Lauren E. Xie, Zhong Perez-Rosello, Tamara Guzman, Jaime N. Surmeier, D. James Kordower, Jeffrey H. Stem Cell Reports Article A major challenge for clinical application of pluripotent stem cell therapy for Parkinson's disease (PD) is large-scale manufacturing and cryopreservation of neurons that can be efficiently prepared with minimal manipulation. To address this obstacle, midbrain dopamine neurons were derived from human induced pluripotent stem cells (iPSC-mDA) and cryopreserved in large production lots for biochemical and transplantation studies. Cryopreserved, post-mitotic iPSC-mDA neurons retained high viability with gene, protein, and electrophysiological signatures consistent with midbrain floor-plate lineage. To test therapeutic efficacy, cryopreserved iPSC-mDA neurons were transplanted without subculturing into the 6-OHDA-lesioned rat and MPTP-lesioned non-human-primate models of PD. Grafted neurons retained midbrain lineage with extensive fiber innervation in both rodents and monkeys. Behavioral assessment in 6-OHDA-lesioned rats demonstrated significant reversal in functional deficits up to 6 months post transplantation with reinnervation of the host striatum and no aberrant growth, supporting the translational development of pluripotent cell-based therapies in PD. Elsevier 2017-06-01 /pmc/articles/PMC5511045/ /pubmed/28579395 http://dx.doi.org/10.1016/j.stemcr.2017.04.033 Text en © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Wakeman, Dustin R. Hiller, Benjamin M. Marmion, David J. McMahon, Christopher W. Corbett, Grant T. Mangan, Kile P. Ma, Junyi Little, Lauren E. Xie, Zhong Perez-Rosello, Tamara Guzman, Jaime N. Surmeier, D. James Kordower, Jeffrey H. Cryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo |
title | Cryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo |
title_full | Cryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo |
title_fullStr | Cryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo |
title_full_unstemmed | Cryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo |
title_short | Cryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo |
title_sort | cryopreservation maintains functionality of human ipsc dopamine neurons and rescues parkinsonian phenotypes in vivo |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511045/ https://www.ncbi.nlm.nih.gov/pubmed/28579395 http://dx.doi.org/10.1016/j.stemcr.2017.04.033 |
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