Abstract
Mesenchymal stem cells (MSCs) hold great promise for the treatment of numerous diseases. A major problem for MSC therapeutic use is represented by the very low amount of MSCs which can be isolated from different tissues; thus ex vivo expansion is indispensable. Long-term culture, however, is associated with extensive morphological and functional changes of MSCs. In addition, the concern that they may accumulate stochastic mutations which lead the risk of malignant transformation still remains. Overall, the genome of human MSCs (hMSCs) appears to be apparently stable throughout culture, though transient clonal aneuploidies have been detected. Particular attention should be given to the use of low-oxygen environment in order to increase the proliferative capacity of hMSCs, since data on the effect of hypoxic culture conditions on genomic stability are few and contradictory. Furthermore, specific and reproducible epigenetic changes were acquired by hMSCs during ex vivo expansion, which may be connected and trigger all the biological changes observed. In this review we address current issues on long-term culture of hMSCs with a 360-degree view, starting from the genomic profiles and back, looking for an epigenetic interpretation of their genetic stability.
Highlights
Mesenchymal stem cells (MSCs) hold great promise for the treatment of numerous diseases
Genomic instability after long-term in vitro culture has been widely described in mouse and rat BM-MSCs [18, 19, 23,24,25], and it has been associated with spontaneous malignant transformation [18, 19, 23, 24]
In adipose tissue stem cells (ASCs) and BM-MSCs OCT4 is silenced by promoter hypermethylation, whereas NANOG and SOX2 are unmethylated despite the repressed state of the genes
Summary
Mesenchymal stem cells (MSCs) are multipotent adult stem cells with a great therapeutic potential in tissue engineering, regenerative medicine, autoimmune diseases, and pathologies characterized by chronic inflammatory processes [1, 2]. A high frequency of detected chromosomal abnormality breakpoints corresponded to common fragile sites (CFSs), in analogy with tumorigenesis [40, 41] Considering these conflicting data, the question is still open and particular attention should be given to the use of low-oxygen environment, through continuous monitoring of the chromosomal stability in addition to the proliferative capacity and differentiation of hMSCs. it should be remembered that the impact of culture condition on epigenetic properties of pluripotent stem cells and preimplantation embryos, for example, has already been established [42]
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