P68Investigation of effects of age on isolation and function of cardiac stem cells

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Abstract

Cardiovascular disease remains the leading cause of morbility and mortality in many parts of the world. There are many risk factors for cardiovascular disease, and age is a major one. Recently, stem cell-based therapy has emerged as a promising approach to cardiac therapy with resident cardiac stem cells (CSCs) representing a desirable candidate because of their endogeneous origin and potential to develop into cardiac lineages. Furthermore, CSCs can be expanded in culture to give sufficient cells for therapy. However, increased age may result in a progressive decline in number and function of available cardiac stem cells. Therefore, the objectives of this study were to investigate the impact of age on CSC isolation and function in vitro.

CSCs were isolated and expanded, via the formation of cardiospheres, from the hearts of C57BL/10 mice at 1.5, 6, 18 and 24 months old. The number and function of explant-derived cells (EDCs) and cardiosphere-derived cells (CDCs) generated were examined. Young mice produced significantly more EDCs and CDCs per mg tissue, compared with 24 months old mice. CDCs derived from 1.5 months old mice exhibited higher expression of cardiac stem cell markers including c-kit and Sca-1 than those from 24 months old mice (c-kit: 13% vs 3%; Sca-1: 83% vs 50%, respectively). EDCs and CDCs from young animals showed increased migration, compared with those from aged ones. Higher proliferative capacity and clonogenic efficiency were also found in CDCs from younger mice. After induction of cardiomyogenic differentiation using either 5-azacytidine or DMSO, it was found that CDCs from young mice expressed a higher percentage of the cardiomyocyte-specific marker - cardiac troponin T.

In conclusion, aged animals generated a reduced number of cardiac stem cells, and the CDCs showed impaired proliferation, migration, clonogenicity and differentiation.

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