The regenerative potential of marrow-derived mesenchymal stem cells (MSCs) exhibits significant variation, particularly among older patients.<b> </b>The objective of this study is to identify a cell-surface marker whose expression is predictive of the in vitro proliferation and differentiation potential of MSCs.<b> </b>This study evaluates surface expression of decoy TRAIL receptor CD264, in vitro regenerative potential and metrics of cellular aging for marrow MSCs from 12 donors, 20-60 years old. Male and female donors were age-matched. When CD264(+) cell content was 20% to 35%, MSC cultures from young (20 &lt; age &lt; 40) and older (45 &lt; age &lt; 60) donors proliferated rapidly and differentiated extensively. Older donor MSCs containing &lt; 35% CD264(+) cells had a small size and negligible senescence despite the donor’s advanced chronological age. Above the 35% threshold, CD264 expression inversely correlated with proliferation and differentiation potential. When CD264(+) cell content was 75%, MSCs were enlarged and mostly senescent with severely compromised regenerative potential. There was no correlation of the older donors’ chronological age to either CD264(+) cell content or the regenerative potential of the donor MSCs. CD264 was upregulated after p53 and had a similar expression profile to that of p21 during serial passage of MSCs. No sex-linked differences were detected in this study. The strong inverse correlation of CD264(+) cell content to the in vitro regenerative potential of MSCs has possible application to predict the therapeutic potential of patient MSCs, and to standardize the composition and efficacy of MSC therapies.

Decoy TRAIL receptor CD264: A predictor of in vitro regenerative potential for mesenchymal stem cells

255th National Meeting (2018)

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