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Chromosomal instability in human mesenchymal stem cells immortalized with human papilloma virus E6, E7, and hTERT genes

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An Erratum to this article was published on 22 September 2007

An Erratum to this article was published on 28 June 2007

Abstract

Human mesenchymal stem cells (hMSCs) are expected to be an enormous potential source for future cell therapy, because of their self-renewing divisions and also because of their multiple-lineage differentiation. The finite lifespan of these cells, however, is a hurdle for clinical application. Recently, several hMSC lines have been established by immortalized human telomerase reverse transcriptase gene (hTERT) alone or with hTERT in combination with human papillomavirus type 16 E6/E7 genes (E6/E7) and human proto-oncogene, Bmi-1, but have not so much been characterized their karyotypic stability in detail during extended lifespan under in vitro conditions. In this report, the cells immortalized with the hTERT gene alone exhibited little change in karyotype, whereas the cells immortalized with E6/E7 plus hTERT genes or Bmi-1, E6 plus hTERT genes were unstable regarding chromosome numbers, which altered markedly during prolonged culture. Interestingly, one unique chromosomal alteration was the preferential loss of chromosome 13 in three cell lines, observed by fluorescence in situ hybridization (FISH) and comparative-genomic hybridization (CGH) analysis. The four cell lines all maintained the ability to differentiate into both osteogenic and adipogenic lineages, and two cell lines underwent neuroblastic differentiation. Thus, our results were able to provide a step forward toward fulfilling the need for a sufficient number of cells for new therapeutic applications, and substantiate that these cell lines are a useful model for understanding the mechanisms of chromosomal instability and differentiation of hMSCs.

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Acknowledgments

This study was supported in part by a grant from the Ministry of Health, Labor and Welfare of Japan. We are grateful to Dr. T.Masui for his advice on ethics problems, and to Mr. H.Migitaka (Carl Zeiss Co., Ltd.) for his assistance with mFISH karyotype analysis. M.T. and K.T. contributed equally to this work.

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Authors and Affiliations

  1. Division of Bioresources, National Institute of Biomedical Innovation, Osaka, 567-0085, Japan

    Masao Takeuchi, Kikuko Takeuchi, Arihiro Kohara, Setsuko Shioda, Yutaka Ozawa, Azusa Ohtani & Hiroshi Mizusawa

  2. Health Science Research Resources Bank, Osaka, 590-0535, Japan

    Motonobu Satoh

  3. National Research Institute for Child Health and Development, Tokyo, 157-8535, Japan

    Keiko Morita, Takashi Hirano & Akihiro Umezawa

  4. Department of Reproductive Biology and Pathology and Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, 157-8535, Japan

    Masanori Terai

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  1. Masao Takeuchi
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Correspondence to Masao Takeuchi.

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Editor: J. Denry Sato

An erratum to this article can be found at http://dx.doi.org/10.1007/s11626-007-9057-x

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Takeuchi, M., Takeuchi, K., Kohara, A. et al. Chromosomal instability in human mesenchymal stem cells immortalized with human papilloma virus E6, E7, and hTERT genes. In Vitro Cell.Dev.Biol.-Animal 43, 129–138 (2007). https://doi.org/10.1007/s11626-007-9021-9

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