Mechanisms of action of mesenchymal stem cells in cardiac repair: Potential influences on the cardiac stem cell niche

Ramesh Mazhari, Joshua Hare

Research output: Contribution to journalArticle

160 Citations (Scopus)

Abstract

Clinical and basic studies of cell-based myocardial therapy have proceeded at a rapid pace. Cell therapy could lead to successful cardiac regeneration or repair by any of three general mechanisms: differentiation of the administered cells into all of the cellular constituents of the heart; release of factors capable of paracrine signaling from the administered cells; and fusion of the administered cells with the existing constituents of the heart. Here, we argue that a fourth general mechanism could be operative: stimulation of endogenous repair by injected cells, which and might cause the regeneration of stem cell niches. In a porcine model of myocardial infarction, allogeneic mesenchymal stem cells stimulated substantial improvement in the ejection fraction, reduction of infarct size, and the growth of a rim of new cardiac tissue in the region in which the mesenchymal stem cells were injected. These effects occurred in the absence of definitive cardiac myocyte differentiation. After myocardial infarction, porcine hearts exhibit evidence of cardiac myocytes that have entered the cell cycle, neovascularization, and reduced levels of apoptosis. These data, in addition to new insights regarding the presence of endogenous cardiac stem cells, strongly support the concept that the heart could contain stem cell niches. Effective cell therapy could lead to restoration of these niches through multifaceted cell-cell interactions.

Original languageEnglish
JournalNature Clinical Practice Cardiovascular Medicine
Volume4
Issue numberSUPPL. 1
DOIs
StatePublished - Feb 1 2007
Externally publishedYes

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Stem Cell Niche
Mesenchymal Stromal Cells
Cell- and Tissue-Based Therapy
Cardiac Myocytes
Regeneration
Swine
Myocardial Infarction
Paracrine Communication
Cell Fusion
Cell Communication
Cell Differentiation
Cell Cycle
Stem Cells
Apoptosis
Growth

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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