Mesenchymal stromal cells are genetically stable under a hostile in vivo-like scenario as revealed by in vitro micronucleus test

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• 作者：Shikha Sharma ; Ramesh Bhonde ; ^{rr.bhonde@manipal.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Nuclear blebs ; micronuclei ; hypoxia ; high glucoose ; ischemia ; mesenchymal stem cells
• 刊名：Cytotherapy
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：17
• 期：10
• 页码：1384-1395
• 全文大小：3544 K

文摘

Mesenchymal stromal cells (MSCs) have elicited a great hope in the field of regenerative medicine because of their high therapeutic potential in treating several disorders. Therefore, from the clinical point of view, it is essential to understand genetic stability and survival of MSCs under different in vivo scenarios. Recently, we have reported nuclear blebs and micronuclei as a marker of genetic instability in MSCs.

Methods

In our present study, we exposed umbilical cord MSCs and placenta-derived MSCs to diverse conditions simulating an in vivo scenario and studied their genetic stability by use of an in vitro micronucleus test.

Results

We observed that a sudden decrease in oxygen concentration led to an increase in the number of nuclear blebs and decrease in proliferation rate without inducing senescence. Moreover, we also observed that 2.5% hypoxia exerted a markedly different pattern of regulation of various cell cycle checkpoint genes such as hypoxia-inducible factor-1伪 (HIF-1伪), ataxia telangiectasia mutated (ATM), ataxia telangiectasia and Rad3 related (ATR), p53, p21, p27 and p21 than did 5% hypoxia. It is interesting to note that the MSCs were genetically stable under hyperglycemic and ischemic conditions and underwent quiescence on serum starvation accompanied by hypoxia. We also tested the genotoxicity of conditioned media derived from adverse conditions and observed that it did not result in genetic instability.

Conclusions

Our data demonstrate for the first time that umbilical MSCs and placenta-derived MSCs are genetically stable under hostile in vivo situations, indicating their suitability for therapeutic purposes.