An appraisal of genetic stability in human mesenchymal stem cells

Human bone-marrow mesenchymal stem cells (BM MSCs) and adipose derived stem cells (ADSCs) were evaluated for evidence of senescence during exposure to hypoxic conditions and protracted ex vivo expansion. Under hypoxia we have observed microsatellite instability and down-regulation of genes involved in DNA repair. Simultaneously, a decrease in ATP content and in the number of mitochondrial genomes was observed. Irrespective of O2 tension or cell passage, we observed several heteroplasmic point mutations, some of which have been reported in a wide range of tumors. These results alert for a careful analysis of cell integrity during the development and application of regenerative therapies.