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

Background aims. 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 alpha (HIF-1 alpha), 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 geno-toxicity 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.