title: Aging Impairs the Proliferative Capacity of Cardiospheres, Cardiac Progenitor Cells and Cardiac Fibroblasts: Implications for Cell Therapy.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Medicine, Division of Cardiology, University of California San Francisco, San Francisco, CA 94143, USA. jianqiny@medicine.ucsf.edu.
authors.forename: Jianqin
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Medicine, Division of Cardiology, University of California San Francisco, San Francisco, CA 94143, USA. douglas.hom@gmail.com.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Hom
authors.affiliation: Department of Medicine, Division of Cardiology, University of California San Francisco, San Francisco, CA 94143, USA. joy.hwang.ucsf@gmail.com.
authors.forename: Joy
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Department of Medicine, Division of Cardiology, University of California San Francisco, San Francisco, CA 94143, USA. yeghiaza@medicine.ucsf.edu.|Edyth and Eli Broad Center for Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143, USA. yeghiaza@medicine.ucsf.edu.
authors.forename: Yerem
authors.initials: Y
authors.lastname: Yeghiazarians
authors.affiliation: Department of Medicine, Division of Cardiology, University of California San Francisco, San Francisco, CA 94143, USA. lee@medicine.ucsf.edu.|Edyth and Eli Broad Center for Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143, USA. lee@medicine.ucsf.edu.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Lee
authors.affiliation: Department of Medicine, Division of Cardiology, University of California San Francisco, San Francisco, CA 94143, USA. andrewboyle500@gmail.com.|Edyth and Eli Broad Center for Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143, USA. andrewboyle500@gmail.com.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Boyle
keywords: aging; cardiac fibroblast; cardiac progenitor cell; paracrine signaling; proliferation