J. Clin. Med. 2013, 2(3), 103-114; doi:10.3390/jcm2030103
Article

Aging Impairs the Proliferative Capacity of Cardiospheres, Cardiac Progenitor Cells and Cardiac Fibroblasts: Implications for Cell Therapy

1 Department of Medicine, Division of Cardiology, University of California San Francisco, San Francisco, CA 94143, USA 2 Edyth and Eli Broad Center for Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143, USA These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 31 July 2013; in revised form: 9 August 2013 / Accepted: 22 August 2013 / Published: 23 September 2013
(This article belongs to the Special Issue Frontiers in Stem Cell Treatments)
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Abstract: Introduction: Cardiospheres (CS) are self-assembling clusters of cells that can be grown from cardiac tissue. They contain a heterogeneous cell population that includes cardiac progenitor cells (CPCs) and cardiac fibroblasts. CS and CPCs have been shown to improve cardiac function after myocardial infarction (MI) in experimental models and are now being studied in clinical trials. The effects of aging on the proliferative capacity of CS and CPCs, and the paracrine signaling between cell types, remain incompletely understood. Methods and Results: We compared the growth of CS from young and aging murine hearts at baseline and following MI. The number of CS from young and aging hearts was similar at baseline. However, after MI, young hearts had a dramatic increase in the number of CS that grew, but this proliferative response to MI was virtually abolished in the aging heart. Further, the proportion of cells within the CS that were CPCs (defined as Sca-1(stem cell antigen-1)+/CD45) was significantly lower in aging hearts than young hearts. Thus the number of available CPCs after culture from aging hearts was substantially lower than from young hearts. Cardiac fibroblasts from aging hearts proliferated more slowly in culture than those from young hearts. We then investigated the interaction between aging cardiac fibroblasts and CPCs. We found no significant paracrine effects on proliferation between these cell types, suggesting the impaired proliferation is a cell-autonomous problem. Conclusions: Aging hearts generate fewer CPCs, and aging CPCs have significantly reduced proliferative potential following MI. Aging cardiac fibroblasts also have reduced proliferative capacity, but these appear to be cell-autonomous problems, not caused by paracrine signaling between cell types.
Keywords: cardiac progenitor cell; aging; cardiac fibroblast; proliferation; paracrine signaling

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MDPI and ACS Style

Ye, J.; Hom, D.S.; Hwang, J.; Yeghiazarians, Y.; Lee, R.J.; Boyle, A.J. Aging Impairs the Proliferative Capacity of Cardiospheres, Cardiac Progenitor Cells and Cardiac Fibroblasts: Implications for Cell Therapy. J. Clin. Med. 2013, 2, 103-114.

AMA Style

Ye J, Hom DS, Hwang J, Yeghiazarians Y, Lee RJ, Boyle AJ. Aging Impairs the Proliferative Capacity of Cardiospheres, Cardiac Progenitor Cells and Cardiac Fibroblasts: Implications for Cell Therapy. Journal of Clinical Medicine. 2013; 2(3):103-114.

Chicago/Turabian Style

Ye, Jianqin; Hom, Douglas S.; Hwang, Joy; Yeghiazarians, Yerem; Lee, Randall J.; Boyle, Andrew J. 2013. "Aging Impairs the Proliferative Capacity of Cardiospheres, Cardiac Progenitor Cells and Cardiac Fibroblasts: Implications for Cell Therapy." J. Clin. Med. 2, no. 3: 103-114.

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