Basic Research in Cardiology

, 109:443

Cardiospheres reverse adverse remodeling in chronic rat myocardial infarction: roles of soluble endoglin and Tgf-β signaling

  • Eleni Tseliou
  • Heidi Reich
  • Geoffrey de Couto
  • John Terrovitis
  • Baiming Sun
  • Weixin Liu
  • Eduardo Marbán
Original Contribution

DOI: 10.1007/s00395-014-0443-8

Cite this article as:
Tseliou, E., Reich, H., de Couto, G. et al. Basic Res Cardiol (2014) 109: 443. doi:10.1007/s00395-014-0443-8

Abstract

Self-assembling heart-derived stem cell clusters named cardiospheres (CSps) improve function and attenuate remodeling in rodent models of acute myocardial infarction. The effects of CSps in chronically remodeled myocardium post-MI, and the underlying mechanisms, remain unknown. One month after permanent coronary ligation, rats were randomly assigned to injection of vehicle (controls) or CSps in the peri-infarct area. One month post-injection, CSps increased left ventricular function, reduced scar mass and collagen density, and enhanced vascularity within the infarct zone compared to controls. Immunoblots revealed Tgfβ-1/smad cascade downregulation and an increase in soluble endoglin post-CSp injection. Six months post-transplantation, left ventricular function further improved and cardiomyocyte hypertrophy was attenuated in the CSp-treated group. In vitro, co-culture of CSps with fibroblasts recapitulated the suppression of the Tgf-β1/smad pathway changes, responses which were blunted by neutralizing antibody against endoglin. Thus, cardiosphere transplantation enhances angiogenesis and reduces fibrosis in chronically infarcted myocardium, leading to partial reversal of cardiac dysfunction. The underlying mechanism involves inhibition of Tgf-β1/smad signaling by CSp-secreted soluble endoglin.

Keywords

Stem cellsChronic ischemic cardiomyopathyCardiac regenerationCardiac fibrosis

Supplementary material

395_2014_443_MOESM1_ESM.docx (1.7 mb)
Supplementary material 1 (DOCX 1730 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Eleni Tseliou
    • 1
  • Heidi Reich
    • 1
  • Geoffrey de Couto
    • 1
  • John Terrovitis
    • 2
  • Baiming Sun
    • 1
  • Weixin Liu
    • 1
  • Eduardo Marbán
    • 1
  1. 1.Cedars-Sinai Heart InstituteLos AngelesUSA
  2. 2.Third Department of CardiologyUniversity of AthensAthensGreece