Células-tronco mesenquimais humanas e reparo de DNA: Uma análise in silico de dados de microarray

Abstract

Human mesenchymal stem cells (hMSC) are multipotent stem cells of stromal origin. These cells have been widely used for cell therapy means in regenerative medicine due to their tissue diferentiation capacity as well as in vitro expansion and functional plasticity. The effects of senescence on genetic stability has been discussed througout the years, so that a previous study has found that stem cell senescence is associated with chromossomal abnormalities, which can explain the reason why these cells have been linked to age-related diseases such as cancer and Alzheimer’s disease. Furthermore, genetic instability can be responsible for the acquisition of tumorigenesis features in vitro and in vivo. In this study, the expression of DNA repair pathways of umbilical cord- derived hMSC harboring a paracentric chromosomal inversion (MSC/inv) was compared to a normal karyotype lineage (MSC/n) in early (Passage 9) and late (Passage 18) in vitro passages. Microarray data from these cell groups was analyzed through two in silico approaches: Gene Set Enrichment Analysis (GSEA) and gene prioritization (Endeavour). When compared to young stem cells, our results show that both groups of senescent stem cells present reduced DNA repair expression. By looking at the two groups of young stem cells, we found that there is no differential expression of DNA repair pathways between them, whereas senescent stem cell with inverted karyotype showed lower expression of DNA repair pathways. These findings support the idea that senescence alters DNA repair capacity of CTMs, given the inhibition of several DNA repair pathways, especially on MSCs/inv, which presented accentuated genetic instability.