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In vivo maturation of human embryonic stem cell-derived teratoma over time

Transformation of human embryonic stem cells (hESC) is of interest to scientists who use them as a raw material for cell-processed therapeutic products. However, the WHO and ICH guidelines provide only study design advice and general principles for tumorigenicity tests. In this study, we performed i...

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Autores principales: Akutsu, Hidenori, Nasu, Michiyo, Morinaga, Shojiroh, Motoyama, Teiichi, Homma, Natsumi, Machida, Masakazu, Yamazaki-Inoue, Mayu, Okamura, Kohji, Nakabayashi, Kazuhiko, Takada, Shuji, Nakamura, Naoko, Kanzaki, Seiichi, Hata, Kenichiro, Umezawa, Akihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Japanese Society for Regenerative Medicine 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581884/
https://www.ncbi.nlm.nih.gov/pubmed/31245498
http://dx.doi.org/10.1016/j.reth.2016.06.003
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author Akutsu, Hidenori
Nasu, Michiyo
Morinaga, Shojiroh
Motoyama, Teiichi
Homma, Natsumi
Machida, Masakazu
Yamazaki-Inoue, Mayu
Okamura, Kohji
Nakabayashi, Kazuhiko
Takada, Shuji
Nakamura, Naoko
Kanzaki, Seiichi
Hata, Kenichiro
Umezawa, Akihiro
author_facet Akutsu, Hidenori
Nasu, Michiyo
Morinaga, Shojiroh
Motoyama, Teiichi
Homma, Natsumi
Machida, Masakazu
Yamazaki-Inoue, Mayu
Okamura, Kohji
Nakabayashi, Kazuhiko
Takada, Shuji
Nakamura, Naoko
Kanzaki, Seiichi
Hata, Kenichiro
Umezawa, Akihiro
author_sort Akutsu, Hidenori
collection PubMed
description Transformation of human embryonic stem cells (hESC) is of interest to scientists who use them as a raw material for cell-processed therapeutic products. However, the WHO and ICH guidelines provide only study design advice and general principles for tumorigenicity tests. In this study, we performed in vivo tumorigenicity tests (teratoma formation) and genome-wide sequencing analysis of undifferentiated hESCs i.e. SEES-1, -2 and -3 cells. We followed up with teratoma formation histopathologically after subcutaneous injection of SEES cells into immunodeficient mice in a qualitative manner and investigated the transforming potential of the teratomas. Maturity of SEES-teratomas perceptibly increased after long-term implantation, while areas of each tissue component remained unchanged. We found neither atypical cells/structures nor cancer in the teratomas even after long-term implantation. The teratomas generated by SEES cells matured histologically over time and did not increase in size. We also analyzed genomic structures and sequences of SEES cells during cultivation by SNP bead arrays and next-generation sequencing, respectively. The nucleotide substitution rate was 3.1 × 10(−9), 4.0 × 10(−9), and 4.6 × 10(−9) per each division in SEES-1, SEES-2, and SEES-3 cells, respectively. Heterozygous single-nucleotide variations were detected, but no significant homologous mutations were found. Taken together, these results imply that SEES-1, -2, and -3 cells do not exhibit in vivo transformation and in vitro genomic instability.
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spelling pubmed-65818842019-06-26 In vivo maturation of human embryonic stem cell-derived teratoma over time Akutsu, Hidenori Nasu, Michiyo Morinaga, Shojiroh Motoyama, Teiichi Homma, Natsumi Machida, Masakazu Yamazaki-Inoue, Mayu Okamura, Kohji Nakabayashi, Kazuhiko Takada, Shuji Nakamura, Naoko Kanzaki, Seiichi Hata, Kenichiro Umezawa, Akihiro Regen Ther Original Article Transformation of human embryonic stem cells (hESC) is of interest to scientists who use them as a raw material for cell-processed therapeutic products. However, the WHO and ICH guidelines provide only study design advice and general principles for tumorigenicity tests. In this study, we performed in vivo tumorigenicity tests (teratoma formation) and genome-wide sequencing analysis of undifferentiated hESCs i.e. SEES-1, -2 and -3 cells. We followed up with teratoma formation histopathologically after subcutaneous injection of SEES cells into immunodeficient mice in a qualitative manner and investigated the transforming potential of the teratomas. Maturity of SEES-teratomas perceptibly increased after long-term implantation, while areas of each tissue component remained unchanged. We found neither atypical cells/structures nor cancer in the teratomas even after long-term implantation. The teratomas generated by SEES cells matured histologically over time and did not increase in size. We also analyzed genomic structures and sequences of SEES cells during cultivation by SNP bead arrays and next-generation sequencing, respectively. The nucleotide substitution rate was 3.1 × 10(−9), 4.0 × 10(−9), and 4.6 × 10(−9) per each division in SEES-1, SEES-2, and SEES-3 cells, respectively. Heterozygous single-nucleotide variations were detected, but no significant homologous mutations were found. Taken together, these results imply that SEES-1, -2, and -3 cells do not exhibit in vivo transformation and in vitro genomic instability. Japanese Society for Regenerative Medicine 2016-07-25 /pmc/articles/PMC6581884/ /pubmed/31245498 http://dx.doi.org/10.1016/j.reth.2016.06.003 Text en © 2016, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. 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 Original Article
Akutsu, Hidenori
Nasu, Michiyo
Morinaga, Shojiroh
Motoyama, Teiichi
Homma, Natsumi
Machida, Masakazu
Yamazaki-Inoue, Mayu
Okamura, Kohji
Nakabayashi, Kazuhiko
Takada, Shuji
Nakamura, Naoko
Kanzaki, Seiichi
Hata, Kenichiro
Umezawa, Akihiro
In vivo maturation of human embryonic stem cell-derived teratoma over time
title In vivo maturation of human embryonic stem cell-derived teratoma over time
title_full In vivo maturation of human embryonic stem cell-derived teratoma over time
title_fullStr In vivo maturation of human embryonic stem cell-derived teratoma over time
title_full_unstemmed In vivo maturation of human embryonic stem cell-derived teratoma over time
title_short In vivo maturation of human embryonic stem cell-derived teratoma over time
title_sort in vivo maturation of human embryonic stem cell-derived teratoma over time
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581884/
https://www.ncbi.nlm.nih.gov/pubmed/31245498
http://dx.doi.org/10.1016/j.reth.2016.06.003
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