Increased potency of cardiac stem cells compared with bone marrow mesenchymal stem cells in cardiac repair

Behzad N. Oskouei, Guillaume Lamirault, Chacko Joseph, Adriana V. Treuer, Stephanie Landa, Jose Da Silva, Konstantinos Hatzistergos, Marc Dauer, Wayne Balkan, Ian McNiece, Joshua M. Hare

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Whereas cardiac-derived c-kit+ stem cells (CSCs) and bone marrow-derived mesenchymal stem cells (MSCs) are undergoing clinical trials testing safety and efficacy as a cell-based therapy, the relative therapeutic and biologic efficacy of these two cell types is unknown. We hypothesized that human CSCs have greater ability than MSCs to engraft, differentiate, and improve cardiac function. We compared intramyocardial injection of human fetal CSCs (36,000) with two doses of adult MSCs (36,000 and 1,000,000) or control (phosphate buffered saline) in nonobese diabetic/severe combined immune deficiency mice after coronary artery ligation. The myocardial infarction-induced enlargement in left ventricular chamber dimensions was ameliorated by CSCs (p <.05 for diastolic and systolic volumes), as was the decline in ejection fraction (EF; p <.05). Whereas 1 × 106 MSCs partially ameliorated ventricular remodeling and improved EF to a similar degree as CSCs, 36,000 MSCs did not influence chamber architecture or function. All cell therapies improved myocardial contractility, but CSCs preferentially reduced scar size and reduced vascular afterload. Engraftment and trilineage differentiation was substantially greater with CSCs than with MSCs. Adult-cultured c-kit+ CSCs were less effective than fetal, but were still more potent than high-dose MSCs. These data demonstrate enhanced CSC engraftment, differentiation, and improved cardiac remodeling and function in ischemic heart failure. MSCs required a 30-fold greater dose than CSCs to improve cardiac function and anatomy. Together, these findings demonstrate a greater potency of CSCs than bone marrow MSCs in cardiac repair.

Original languageEnglish (US)
Pages (from-to)116-124
Number of pages9
JournalStem Cells Translational Medicine
Volume1
Issue number2
DOIs
StatePublished - 2012

Keywords

  • c-kit
  • Cardiac
  • Mesenchymal stem cells
  • Myocardial infarction
  • Ventricular remodeling

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology

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    Oskouei, B. N., Lamirault, G., Joseph, C., Treuer, A. V., Landa, S., Da Silva, J., Hatzistergos, K., Dauer, M., Balkan, W., McNiece, I., & Hare, J. M. (2012). Increased potency of cardiac stem cells compared with bone marrow mesenchymal stem cells in cardiac repair. Stem Cells Translational Medicine, 1(2), 116-124. https://doi.org/10.5966/sctm.2011-0015