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Published on: September 14, 2015
Influence of aging on the activity of mice Sca-1+CD31- cardiac stem cells
Qiong Wu1,2,3, Jinxi Zhan1,2,3, Shiming Pu1,2,3
1School of Life Sciences, Guangxi Normal University, Guilin, China.
Abstract:
Therapeutic application of cardiac resident stem/progenitor cells (CSC/CPCs) is limited due to decline of their regenerative potential with donor age. A variety of studies have shown that the cardiac aging was the problem of the stem cells, but little is known about the impact of age on the subgroups CSC/CPCs, the relationship between subgroups CSC/CPCs ageing and age-related dysfunction. Here, we studied Sca-1+CD31- subgroups of CSCs from younger(2~3months) and older(22~24months) age mice, biological differentiation was realized using specific mediums for 14 days to induce cardiomyocyte, smooth muscle cells or endothelial cells and immunostain analysis of differentiated cell resulting were done. Proliferation and cell cycle were measured by flow cytometry assay, then used microarray to dissect variability from younger and older mice. Although the number of CSCs was higher in older mice, the advanced age significantly reduced the differentiation ability into cardiac cell lineages and the proliferation ability. Transcriptional changes in Sca-1+CD31- subgroups of CSCs during aging are related to Vitamin B6 metabolism, circadian rhythm, Tyrosine metabolism, Complement and coagulation cascades. Taking together these results indicate that Cardiac resident stem/progenitor cells have significant differences in their proliferative, pluripotency and gene profiles and those differences are age depending.
Insights
Aging significantly impairs cardiac stem/progenitor cells (CSCs/CPCs), reducing their regenerative potential. This study reveals age-dependent declines in CSC/CPC differentiation and proliferation, impacting cardiac repair.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Aging Research
Background:
- Therapeutic use of cardiac stem/progenitor cells (CSCs/CPCs) is hindered by age-related decline in regenerative capacity.
- While cardiac aging is linked to stem cell dysfunction, the specific impact on CSC/CPC subgroups and their relationship with age-related dysfunction remains unclear.
Purpose of the Study:
- To investigate the impact of aging on specific subgroups of cardiac stem/progenitor cells (CSCs/CPCs).
- To analyze the relationship between CSC/CPC aging and age-related cardiac dysfunction.
- To identify age-dependent changes in CSC/CPC proliferation, differentiation, and gene expression.
Main Methods:
- Isolation and characterization of Sca-1+CD31- CSCs from young and old mice.
- Induction of biological differentiation into cardiomyocyte, smooth muscle, and endothelial lineages over 14 days.
- Assessment of cell proliferation and cell cycle using flow cytometry.
- Microarray analysis to identify age-dependent transcriptional differences.
Main Results:
- Older mice exhibited a higher number of CSCs, but significantly reduced differentiation and proliferation abilities compared to younger mice.
- Age-dependent transcriptional changes in CSCs were associated with Vitamin B6 metabolism, circadian rhythm, Tyrosine metabolism, and complement/coagulation cascades.
- Significant age-dependent differences were observed in the proliferative capacity, pluripotency, and gene profiles of CSCs.
Conclusions:
- Cardiac resident stem/progenitor cells display significant age-dependent variations in their proliferative, differentiation, and gene expression profiles.
- Aging compromises the regenerative potential of CSCs, highlighting the need for age-considerate therapeutic strategies.
- Understanding these age-related changes is crucial for developing effective stem cell-based cardiac therapies.
