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Long-Term Safety Issues of iPSC-Based Cell Therapy in a Spinal Cord Injury Model: Oncogenic Transformation with Epithelial-Mesenchymal Transition

Previously, we described the safety and therapeutic potential of neurospheres (NSs) derived from a human induced pluripotent stem cell (iPSC) clone, 201B7, in a spinal cord injury (SCI) mouse model. However, several safety issues concerning iPSC-based cell therapy remain unresolved. Here, we investi...

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Autores principales: Nori, Satoshi, Okada, Yohei, Nishimura, Soraya, Sasaki, Takashi, Itakura, Go, Kobayashi, Yoshiomi, Renault-Mihara, Francois, Shimizu, Atsushi, Koya, Ikuko, Yoshida, Rei, Kudoh, Jun, Koike, Masato, Uchiyama, Yasuo, Ikeda, Eiji, Toyama, Yoshiaki, Nakamura, Masaya, Okano, Hideyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375796/
https://www.ncbi.nlm.nih.gov/pubmed/25684226
http://dx.doi.org/10.1016/j.stemcr.2015.01.006
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author Nori, Satoshi
Okada, Yohei
Nishimura, Soraya
Sasaki, Takashi
Itakura, Go
Kobayashi, Yoshiomi
Renault-Mihara, Francois
Shimizu, Atsushi
Koya, Ikuko
Yoshida, Rei
Kudoh, Jun
Koike, Masato
Uchiyama, Yasuo
Ikeda, Eiji
Toyama, Yoshiaki
Nakamura, Masaya
Okano, Hideyuki
author_facet Nori, Satoshi
Okada, Yohei
Nishimura, Soraya
Sasaki, Takashi
Itakura, Go
Kobayashi, Yoshiomi
Renault-Mihara, Francois
Shimizu, Atsushi
Koya, Ikuko
Yoshida, Rei
Kudoh, Jun
Koike, Masato
Uchiyama, Yasuo
Ikeda, Eiji
Toyama, Yoshiaki
Nakamura, Masaya
Okano, Hideyuki
author_sort Nori, Satoshi
collection PubMed
description Previously, we described the safety and therapeutic potential of neurospheres (NSs) derived from a human induced pluripotent stem cell (iPSC) clone, 201B7, in a spinal cord injury (SCI) mouse model. However, several safety issues concerning iPSC-based cell therapy remain unresolved. Here, we investigated another iPSC clone, 253G1, that we established by transducing OCT4, SOX2, and KLF4 into adult human dermal fibroblasts collected from the same donor who provided the 201B7 clone. The grafted 253G1-NSs survived, differentiated into three neural lineages, and promoted functional recovery accompanied by stimulated synapse formation 47 days after transplantation. However, long-term observation (for up to 103 days) revealed deteriorated motor function accompanied by tumor formation. The tumors consisted of Nestin(+) undifferentiated neural cells and exhibited activation of the OCT4 transgene. Transcriptome analysis revealed that a heightened mesenchymal transition may have contributed to the progression of tumors derived from grafted cells.
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spelling pubmed-43757962015-04-03 Long-Term Safety Issues of iPSC-Based Cell Therapy in a Spinal Cord Injury Model: Oncogenic Transformation with Epithelial-Mesenchymal Transition Nori, Satoshi Okada, Yohei Nishimura, Soraya Sasaki, Takashi Itakura, Go Kobayashi, Yoshiomi Renault-Mihara, Francois Shimizu, Atsushi Koya, Ikuko Yoshida, Rei Kudoh, Jun Koike, Masato Uchiyama, Yasuo Ikeda, Eiji Toyama, Yoshiaki Nakamura, Masaya Okano, Hideyuki Stem Cell Reports Article Previously, we described the safety and therapeutic potential of neurospheres (NSs) derived from a human induced pluripotent stem cell (iPSC) clone, 201B7, in a spinal cord injury (SCI) mouse model. However, several safety issues concerning iPSC-based cell therapy remain unresolved. Here, we investigated another iPSC clone, 253G1, that we established by transducing OCT4, SOX2, and KLF4 into adult human dermal fibroblasts collected from the same donor who provided the 201B7 clone. The grafted 253G1-NSs survived, differentiated into three neural lineages, and promoted functional recovery accompanied by stimulated synapse formation 47 days after transplantation. However, long-term observation (for up to 103 days) revealed deteriorated motor function accompanied by tumor formation. The tumors consisted of Nestin(+) undifferentiated neural cells and exhibited activation of the OCT4 transgene. Transcriptome analysis revealed that a heightened mesenchymal transition may have contributed to the progression of tumors derived from grafted cells. Elsevier 2015-02-13 /pmc/articles/PMC4375796/ /pubmed/25684226 http://dx.doi.org/10.1016/j.stemcr.2015.01.006 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
spellingShingle Article
Nori, Satoshi
Okada, Yohei
Nishimura, Soraya
Sasaki, Takashi
Itakura, Go
Kobayashi, Yoshiomi
Renault-Mihara, Francois
Shimizu, Atsushi
Koya, Ikuko
Yoshida, Rei
Kudoh, Jun
Koike, Masato
Uchiyama, Yasuo
Ikeda, Eiji
Toyama, Yoshiaki
Nakamura, Masaya
Okano, Hideyuki
Long-Term Safety Issues of iPSC-Based Cell Therapy in a Spinal Cord Injury Model: Oncogenic Transformation with Epithelial-Mesenchymal Transition
title Long-Term Safety Issues of iPSC-Based Cell Therapy in a Spinal Cord Injury Model: Oncogenic Transformation with Epithelial-Mesenchymal Transition
title_full Long-Term Safety Issues of iPSC-Based Cell Therapy in a Spinal Cord Injury Model: Oncogenic Transformation with Epithelial-Mesenchymal Transition
title_fullStr Long-Term Safety Issues of iPSC-Based Cell Therapy in a Spinal Cord Injury Model: Oncogenic Transformation with Epithelial-Mesenchymal Transition
title_full_unstemmed Long-Term Safety Issues of iPSC-Based Cell Therapy in a Spinal Cord Injury Model: Oncogenic Transformation with Epithelial-Mesenchymal Transition
title_short Long-Term Safety Issues of iPSC-Based Cell Therapy in a Spinal Cord Injury Model: Oncogenic Transformation with Epithelial-Mesenchymal Transition
title_sort long-term safety issues of ipsc-based cell therapy in a spinal cord injury model: oncogenic transformation with epithelial-mesenchymal transition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375796/
https://www.ncbi.nlm.nih.gov/pubmed/25684226
http://dx.doi.org/10.1016/j.stemcr.2015.01.006
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