Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782363634052104192 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4375796 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT norisatoshi longtermsafetyissuesofipscbasedcelltherapyinaspinalcordinjurymodeloncogenictransformationwithepithelialmesenchymaltransition AT okadayohei longtermsafetyissuesofipscbasedcelltherapyinaspinalcordinjurymodeloncogenictransformationwithepithelialmesenchymaltransition AT nishimurasoraya longtermsafetyissuesofipscbasedcelltherapyinaspinalcordinjurymodeloncogenictransformationwithepithelialmesenchymaltransition AT sasakitakashi longtermsafetyissuesofipscbasedcelltherapyinaspinalcordinjurymodeloncogenictransformationwithepithelialmesenchymaltransition AT itakurago longtermsafetyissuesofipscbasedcelltherapyinaspinalcordinjurymodeloncogenictransformationwithepithelialmesenchymaltransition AT kobayashiyoshiomi longtermsafetyissuesofipscbasedcelltherapyinaspinalcordinjurymodeloncogenictransformationwithepithelialmesenchymaltransition AT renaultmiharafrancois longtermsafetyissuesofipscbasedcelltherapyinaspinalcordinjurymodeloncogenictransformationwithepithelialmesenchymaltransition AT shimizuatsushi longtermsafetyissuesofipscbasedcelltherapyinaspinalcordinjurymodeloncogenictransformationwithepithelialmesenchymaltransition AT koyaikuko longtermsafetyissuesofipscbasedcelltherapyinaspinalcordinjurymodeloncogenictransformationwithepithelialmesenchymaltransition AT yoshidarei longtermsafetyissuesofipscbasedcelltherapyinaspinalcordinjurymodeloncogenictransformationwithepithelialmesenchymaltransition AT kudohjun longtermsafetyissuesofipscbasedcelltherapyinaspinalcordinjurymodeloncogenictransformationwithepithelialmesenchymaltransition AT koikemasato longtermsafetyissuesofipscbasedcelltherapyinaspinalcordinjurymodeloncogenictransformationwithepithelialmesenchymaltransition AT uchiyamayasuo longtermsafetyissuesofipscbasedcelltherapyinaspinalcordinjurymodeloncogenictransformationwithepithelialmesenchymaltransition AT ikedaeiji longtermsafetyissuesofipscbasedcelltherapyinaspinalcordinjurymodeloncogenictransformationwithepithelialmesenchymaltransition AT toyamayoshiaki longtermsafetyissuesofipscbasedcelltherapyinaspinalcordinjurymodeloncogenictransformationwithepithelialmesenchymaltransition AT nakamuramasaya longtermsafetyissuesofipscbasedcelltherapyinaspinalcordinjurymodeloncogenictransformationwithepithelialmesenchymaltransition AT okanohideyuki longtermsafetyissuesofipscbasedcelltherapyinaspinalcordinjurymodeloncogenictransformationwithepithelialmesenchymaltransition |