Chromosomal Instability but Lack of Transformation in Human Myoblast Preparations
Genetic alterations have recently been described as emerging during the culture of embryonic stem cells or induced pluripotent stem cells, raising concerns about their safety in future clinical use. Myoblasts are adult stem cells with important therapeutic potential that have been used in clinical t...
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doaj-bc9ced0632c54c71850396f0dae6c7c02020-11-25T03:24:25ZengSAGE PublishingCell Transplantation0963-68971555-38922014-12-012310.3727/096368913X670192Chromosomal Instability but Lack of Transformation in Human Myoblast PreparationsAurélie Bisson0Stéphanie Le Corre1Géraldine Joly-Helas2Pascal Chambon3Laetitia Demoulins4Laetitia Jean5Sahil Adriouch6Laurent Drouot7Camille Giverne8Francis Roussel9Serge Jacquot10Christelle Doucet11Francis Michot12Marek Lamacz13Thierry Frébourg14Jean-Michel Flaman15Olivier Boyer16Celogos, Paris, FranceRouen University Hospital, Laboratory of Biotherapy, Rouen, FranceRouen University Hospital, Department of Cytogenetics, Rouen, FranceInserm, U1079, Rouen, FranceRouen University Hospital, Laboratory of Biotherapy, Rouen, FranceNormandy University, IRIB, Rouen, FranceNormandy University, IRIB, Rouen, FranceNormandy University, IRIB, Rouen, FranceRouen University Hospital, Laboratory of Biotherapy, Rouen, FranceRouen University Hospital, Department of Pathology, Rouen, FranceRouen University Hospital, Laboratory of Biotherapy, Rouen, FranceCelogos, Paris, FranceRouen University Hospital, Department of Digestive Surgery, Rouen, FranceNormandy University, IRIB, Rouen, FranceRouen University Hospital, Department of Genetics, Rouen, FranceRouen University Hospital, Department of Genetics, Rouen, FranceRouen University Hospital, Laboratory of Biotherapy, Rouen, FranceGenetic alterations have recently been described as emerging during the culture of embryonic stem cells or induced pluripotent stem cells, raising concerns about their safety in future clinical use. Myoblasts are adult stem cells with important therapeutic potential that have been used in clinical trials for almost 20 years, but their genome integrity has not yet been established. Here we produced 10 human myoblast preparations and investigated their genomic stability. At the third passage, half of the preparations had a normal karyotype and half showed one to four alterations/30 metaphases. Chromosome 2 trisomy was found in 1–2/30 meta-phases and/or 2/100 nuclei by FISH in 3/10 samples, and there was no other recurrent anomaly. When prolonging cultures, these erratic abnormalities were never associated with a growth advantage. Cellular senescence was manifested in all samples by growth arrest before passage 15. Expression of TERT was always negative. Molecular analysis of individual p53 transcripts did not reveal tumorigenic mutations. CGH array (10 samples) and exome sequencing (one sample) failed to detect copy number variations or accumulation of mutations, respectively. Myoblasts did not grow either in soft agar or in vivo after injection in immunodeficient mice. Hence, occasional genomic abnormalities may occur during myoblast culture but are not associated with risk of transformation.https://doi.org/10.3727/096368913X670192 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aurélie Bisson Stéphanie Le Corre Géraldine Joly-Helas Pascal Chambon Laetitia Demoulins Laetitia Jean Sahil Adriouch Laurent Drouot Camille Giverne Francis Roussel Serge Jacquot Christelle Doucet Francis Michot Marek Lamacz Thierry Frébourg Jean-Michel Flaman Olivier Boyer |
spellingShingle |
Aurélie Bisson Stéphanie Le Corre Géraldine Joly-Helas Pascal Chambon Laetitia Demoulins Laetitia Jean Sahil Adriouch Laurent Drouot Camille Giverne Francis Roussel Serge Jacquot Christelle Doucet Francis Michot Marek Lamacz Thierry Frébourg Jean-Michel Flaman Olivier Boyer Chromosomal Instability but Lack of Transformation in Human Myoblast Preparations Cell Transplantation |
author_facet |
Aurélie Bisson Stéphanie Le Corre Géraldine Joly-Helas Pascal Chambon Laetitia Demoulins Laetitia Jean Sahil Adriouch Laurent Drouot Camille Giverne Francis Roussel Serge Jacquot Christelle Doucet Francis Michot Marek Lamacz Thierry Frébourg Jean-Michel Flaman Olivier Boyer |
author_sort |
Aurélie Bisson |
title |
Chromosomal Instability but Lack of Transformation in Human Myoblast Preparations |
title_short |
Chromosomal Instability but Lack of Transformation in Human Myoblast Preparations |
title_full |
Chromosomal Instability but Lack of Transformation in Human Myoblast Preparations |
title_fullStr |
Chromosomal Instability but Lack of Transformation in Human Myoblast Preparations |
title_full_unstemmed |
Chromosomal Instability but Lack of Transformation in Human Myoblast Preparations |
title_sort |
chromosomal instability but lack of transformation in human myoblast preparations |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2014-12-01 |
description |
Genetic alterations have recently been described as emerging during the culture of embryonic stem cells or induced pluripotent stem cells, raising concerns about their safety in future clinical use. Myoblasts are adult stem cells with important therapeutic potential that have been used in clinical trials for almost 20 years, but their genome integrity has not yet been established. Here we produced 10 human myoblast preparations and investigated their genomic stability. At the third passage, half of the preparations had a normal karyotype and half showed one to four alterations/30 metaphases. Chromosome 2 trisomy was found in 1–2/30 meta-phases and/or 2/100 nuclei by FISH in 3/10 samples, and there was no other recurrent anomaly. When prolonging cultures, these erratic abnormalities were never associated with a growth advantage. Cellular senescence was manifested in all samples by growth arrest before passage 15. Expression of TERT was always negative. Molecular analysis of individual p53 transcripts did not reveal tumorigenic mutations. CGH array (10 samples) and exome sequencing (one sample) failed to detect copy number variations or accumulation of mutations, respectively. Myoblasts did not grow either in soft agar or in vivo after injection in immunodeficient mice. Hence, occasional genomic abnormalities may occur during myoblast culture but are not associated with risk of transformation. |
url |
https://doi.org/10.3727/096368913X670192 |
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