Abstract
BackgroundMesenchymal stem cells (MSCs) are a mixture of progenitors that are heterogeneous in their regenerative potential. Development of MSC therapies with consistent efficacy is hindered by the absence of an immunophenotype of MSC heterogeneity. This study evaluates decoy TRAIL receptor CD264 as potentially the first surface marker to detect cellular aging in heterogeneous MSC cultures.MethodsCD264 surface expression, regenerative potential, and metrics of cellular aging were assessed in vitro for marrow MSCs from 12 donors ages 20–60 years old. Male and female donors were age matched.Expression of CD264 was compared with that of p16, p21, and p53 during serial passage of MSCs.ResultsWhen CD264+ cell content was 20% to 35%, MSC cultures from young (ages 20–40 years) and older (ages 45–60 years) donors proliferated rapidly and differentiated extensively. Older donor MSCs containing < 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.ConclusionsThese results suggest that CD264 is a surface marker of cellular age for MSCs, not the chronological age of the MSC donor. CD264 is first upregulated in MSCs at an intermediate stage of cellular aging and remains upregulated as aging progresses towards senescence. The strong inverse correlation of CD264+ cell content to the regenerative potential of MSCs has possible application to assess the therapeutic potential of patient MSCs, standardize the composition and efficacy of MSC therapies, and facilitate aging research on MSCs.
Highlights
Mesenchymal stem cells (MSCs) are a mixture of progenitors that are heterogeneous in their regenerative potential
CD264 detects variation in morphology and SA β-Gal activity of MSCs from older donors Figure 1a depicts the variation in the content of CD264+ cells in bone marrow MSC cultures from donors, 45 to 60 years old (n = 6)
The percentage of CD264+ MSCs in culture was independent of chronological age and sex for the older donor group
Summary
Mesenchymal stem cells (MSCs) are a mixture of progenitors that are heterogeneous in their regenerative potential. This study evaluates decoy TRAIL receptor CD264 as potentially the first surface marker to detect cellular aging in heterogeneous MSC cultures. The remarkable regenerative capacity and numerous therapeutic applications of mesenchymal stem cells (MSCs) are well documented [1, 2]; the underlying cellular heterogeneity of MSCs remains a major impediment to the standardization and optimization of MSC therapies for clinical use. Differences in the composition of MSC populations among subjects can compound genotypic differences, giving rise to donor-todonor variation in the function of MSC cultures [9]. It is infeasible at present to standardize the composition of cell populations in MSC therapies because an immunophenotype to characterize MSC heterogeneity is poorly defined [8]. Identifying surface markers for specific MSC populations is an initial step toward the production of MSC therapies with consistent efficacy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
