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Assessment of the Immunomodulatory Properties of Human Mesenchymal Stem Cells MSCs
Published on: December 24, 2015
Decoy TRAIL receptor CD264: a cell surface marker of cellular aging for human bone marrow-derived mesenchymal stem
Sean D Madsen1,2,3, Katie C Russell1,2,3, H Alan Tucker3
1Department of Chemical and Biomolecular Engineering, Tulane University, New Orleans, Louisiana, USA.
Background:
Mesenchymal 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.
Methods:
CD264 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.
Results:
When 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.
Conclusions:
These 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.
Insights
CD264 identifies cellular aging in mesenchymal stem cells (MSCs), not donor age. This marker predicts MSC regenerative potential, aiding in therapy standardization and aging research.
Area of Science:
- Stem Cell Biology
- Cellular Aging
- Immunophenotyping
Background:
- Mesenchymal stem cells (MSCs) are heterogeneous, impacting therapy efficacy.
- Lack of immunophenotype for MSC heterogeneity hinders consistent therapeutic outcomes.
- Decoy TRAIL receptor CD264 is investigated as a marker for cellular aging in MSCs.
Purpose of the Study:
- To evaluate CD264 as a surface marker for detecting cellular aging in heterogeneous MSC cultures.
- To correlate CD264 expression with MSC regenerative potential and aging metrics.
- To determine if CD264 reflects cellular age or donor's chronological age.
Main Methods:
- Assessed CD264 surface expression, regenerative potential, and aging metrics in vitro for MSCs from 12 donors (ages 20-60).
- Compared CD264 expression with p16, p21, and p53 during serial MSC passage.
- Analyzed MSCs based on CD264+ cell content, proliferation, differentiation, and senescence.
Main Results:
- MSC cultures with 20-35% CD264+ cells showed rapid proliferation and differentiation.
- Above 35% CD264+ threshold, expression inversely correlated with proliferation and differentiation.
- 75% CD264+ MSCs were enlarged, senescent, with compromised potential; no correlation with donor chronological age.
- CD264 upregulated after p53 and paralleled p21 expression during serial passage.
Conclusions:
- CD264 serves as a surface marker for MSC cellular age, independent of donor chronological age.
- CD264 is upregulated during intermediate MSC aging and remains high as senescence progresses.
- CD264+ cell content strongly inversely correlates with MSC regenerative potential, useful for therapy assessment and aging research.
