Human mesenchymal stem cell-replicative senescence and oxidative stress are closely linked to aneuploidy.

ABSTRACT: In most clinical trials, human mesenchymal stem cells (hMSCs) are expanded in vitro before implantation. The genetic stability of human stem cells is critical for their clinical use. However, the relationship between stem-cell expansion and genetic stability is poorly understood. Here, we demonstrate that within the normal expansion period, hMSC cultures show a high percentage of aneuploid cells that progressively increases until senescence. Despite this accumulation, we show that in a heterogeneous culture the senescence-prone hMSC subpopulation has a lower proliferation potential and a higher incidence of aneuploidy than the non-senescent subpopulation. We further show that senescence is linked to a novel transcriptional signature that includes a set of genes implicated in ploidy control

SUBMITTER: Estrada JC 

PROVIDER: S-EPMC3702285 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature