HighOCT4and Lowp16INK4AExpressions DetermineIn VitroLifespan of Mesenchymal Stem Cells

[摘要] After long-term culture, mesenchymal stem cells alter their biological properties and enter into a state of replicative senescence. Although several classical biomarkers have been used for quantitative assessment of cellular senescence, no hallmark has been proven completely unique to the senescent state in cells. We used bone marrow-derived MSCs (BM-MSCs) from different healthy young donors and anin vitromodel with well-defined senescence end points to identify a set of robust markers that could potentially predict the expansion capacity of MSCs preparations before reaching senescence. For each early passage BM-MSC sample (5th or 6th passages), the normalized protein expression levels of senescence-associated markersp16INK4A,p21WAF1, SOD2, andrpS6S240/244;the concentration of IL6 and IL8 in cell culture supernatants; and the normalized gene expression levels of pluripotency markersOCT4,NANOG, andSOX2were correlated with final population doubling (PD) number. We revealed that the low expression ofp16INK4Aprotein and a highOCT4gene expression, rather than other evaluated markers, might be potential hallmarks and predictors of greaterin vitrolifespan and growth potential, factors that can impact the successful therapeutic use of MSCs preparations.

[学科分类] 生物技术