Journal
EXPERIMENTAL CELL RESEARCH
Volume 317, Issue 20, Pages 2950-2957Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2011.09.008
Keywords
Cynomolgus monkey; Mesenchymal stem cells; Transformation; Ex vivo expansion; Safety
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Funding
- National Basic Research Program of China [2007CB947704, 2011CB965103]
- National Science Foundation of China [31070946]
- Anhui Medical University [XJ201008]
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Mesenchymal stem cells (MSCs) have shown potential clinical utility in cell therapy and tissue engineering, due to their ability to proliferate as well as to differentiate into multiple lineages, including osteogenic, adipogenic, and chondrogenic specifications. Therefore, it is crucial to assess the safety of MSCs while extensive expansion ex vivo is a prerequisite to obtain the cell numbers for cell transplantation. Here we show that MSCs derived from adult cynomolgus monkey can undergo spontaneous transformation following in vitro culture. In comparison with MSCs, the spontaneously transformed mesenchymal cells (TMCs) display significantly different growth pattern and morphology, reminiscent of the characteristics of tumor cells. Importantly, TMCs are highly tumorigenic, causing subcutaneous tumors when injected into NOD/SCID mice. Moreover, no multiple differentiation potential of TMCs is observed in vitro or in vivo, suggesting that spontaneously transformed adult stem cells may not necessarily turn into cancer stem cells. These data indicate a direct transformation of cynomolgus monkey MSCs into tumor cells following long-term expansion in vitro. The spontaneous transformation of the cultured cynomolgus monkey MSCs may have important implications for ongoing clinical trials and for models of oncogenesis, thus warranting a more strict assessment of MSCs prior to cell therapy. (C) 2011 Elsevier Inc. All rights reserved.
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