Assessment of tumourigenic potential in long-term cryopreserved human adipose-derived stem cells

Document Type

Article

Publication Date

1-1-2016

Abstract

Cryopreservation represents an efficient way to preserve human mesenchymal stem cells (hMSCs) at early culture/passage, and allows pooling of cells to achieve sufficient cells required for off-the-shelf use in clinical applications, e.g. cell-based therapies and regenerative medicine. To fully apply cryopreserved hMSCs in a clinical setting, it is necessary to evaluate their biosafety, e.g. chromosomal abnormality and tumourigenic potential. To date, many studies have demonstrated that cryopreserved hMSCs display no chromosomal abnormalities. However, the tumourigenic potential of cryopreserved hMSCs has not yet been evaluated. In the present study, we cryopreserved human adipose-derived mesenchymal stem cells (hASCs) for 3 months, using a slow freezing method with various cryoprotective agents (CPAs), followed by assessment of the tumourigenic potential of the cryopreserved hASCs after thawing and subculture. We found that long-term cryopreserved hASCs maintained normal levels of the tumour suppressor markers p53, p21, p16 and pRb, hTERT, telomerase activity and telomere length. Further, we did not observe significant DNA damage or signs of p53 mutation in cryopreserved hASCs. Our findings suggest that long-term cryopreserved hASCs are at low risk of tumourigenesis. These findings aid in establishing the biosafety profile of cryopreserved hASCs, and thus establishing low hazardous risk perception with the use of long-term cryopreserved hASCs for future clinical applications.

Keywords

Biosafety, Clinical applications, Human adipose-derived stem cells, Long-term cryopreservation, Low risk, Tumourigenic potential assessment

Divisions

fac_eng,fac_med

Funders

Ministry of Education of Malaysia and University of Malaya [High Impact Research Grant No. UM.C/HIR/MOHE/ENG/44 and Postgraduate Research Grant (PPP) No. PG007-2014A],National Natural Science Foundation of China (Grant Nos 11372243 and 81401270),International Science and Technology Cooperation Programme of China (Grant No. 2013DFG02930),Key Programme for International S&T Cooperation Projects of Shaanxi (Grant No. 2013KW33-01)

Publication Title

Journal of Tissue Engineering and Regenerative Medicine

Volume

11

Issue

8

Publisher

Wiley

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