Dose-dependent functional benefit of human cardiosphere transplantation in mice with acute myocardial infarction

Deliang Shen, Ke Cheng, Eduardo Marbán

Research output: Contribution to journalArticle

Abstract

Despite mounting pre-clinical and clinical evidence of the beneficial effects of cell-based therapy, optimal cell dosing and delivery approaches have not been identified. Cardiospheres are self-assembling three-dimensional (3D) microtissues formed by cardiac stem cells and supporting cell types. The ability of cardiospheres to augment cardiac function has been demonstrated in animal models of ischemic cardiomyopathy. In this study, we studied the dose dependence of the benefits of human cardiospheres, delivered via intramyocardial injection, upon cardiac function and ventricular remodelling in SCID mice with acute myocardial infarction. Four doses of cardiospheres were used: 1 × 104, 5 × 104, 1 × 105 and 5 × 105 (expressed as number of plated cardiosphere-forming cells). Acute (24 hr) cell retention rates in all groups were similar. Functional assessment and quantitative heart morphometry indicated benefit from higher cell doses (≥5 × 104) in terms of ejection fraction, infarct size and capillary density. Histological analysis indicated that the dose-dependent benefit was primarily because of indirect effects of transplanted cells. The results provide scalable data on cardiosphere dosing for intramyocardial injection.

Original languageEnglish (US)
Pages (from-to)2112-2116
Number of pages5
JournalJournal of Cellular and Molecular Medicine
Volume16
Issue number9
DOIs
Publication statusPublished - Sep 2012
Externally publishedYes

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Keywords

  • Cardiospheres
  • Cell transplantation
  • Dose effects
  • Myocardial infarction
  • Stem cells

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

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