Changes in CDKN2D,TP53, and miR125a expression: potential role in the evaluation of human amniotic fluid‐derived mesenchymal stromal cell fitness

Abstract

Human amniotic fluid-derived mesenchymal stromal cells (hAMSC) have become one of the main cell populations used in regenerative medicine and for the study of various clinical disorders. These cells have a great capacity for proliferation and differentiation and do not form teratomas when transplanted into animal models, and their stemness seems to be between embryonic cells and adult mesenchymal cells. Before their use in cell therapy, they must be cultured and expanded in vitro, but the effect this process has on their fitness, a determining factor for the success or failure of cell therapy, is unknown. We undertook a follow-up of gene and microRNAs (miRNAs) expression using microarray of hAMSC for the first 15 passages. Significant changes were noted in the expression of various mRNAs and miRNAs, particularly down-regulation of TP53, increased expression of hsa-miR-125a and up-regulation of CDKN2D. The variations in TP53 and hsa-miR-125a may act as an indicator of the stemness of the hAMSC, whereas CDKN2D may indicate the begging of early senescence process in a p53-independent mechanism. The genes described in this study will help evaluate the fitness of hAMSC, thus guaranteeing their biological quality for use in regenerative medicine.

Amniotic Fluid Cells, Stem Cells, and p53: Can We Stereotype p53 Functions?

“…Earlier reports showed both constant stable expression and also downregulation of p53 mRNA during long term passaging of AFS cells and AF mesenchymal stromal/stem cells [14,113,114]. In our hands, expression of p53 did not change with increased passaging numbers of AFS cells, which is consistent with the studies of Poloni et al and Phermthai et al [14,113].…”

Gestational diabetes and maternal obesity are associated with sex-specific changes in miRNA and target gene expression in the fetus

“…Eighty-eight miRNA candidates were generated from a PubMed literature review with search terms including "miRNA" and "Type I and Type 2 diabetes, GDM, preeclampsia, adipogenesis, obesity, and nonalcoholic fatty liver disease" 13,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] (Supplemental Table 1). Individual candidate miRNA abundance was measured via Multiplex Circulating miRNA assay (Abcam, FirePlex, Cambridge, MA).…”

LncRNA CRNDE promotes the progression and angiogenesis of pancreatic cancer via miR-451a/CDKN2D axis

“…CDKN2D acts as an inhibitor of cyclin D-dependent kinases [ 21 ]. In addition, CDKN2D plays a critical role in the regulation of tumor growth [ 20 ]. For example, CDKN2D regulates both cell proliferation and granulocytic differentiation in acute promyelocytic leukemia cells [ 30 ].…”