Concise review: The role of clinical trials in deciphering mechanisms of action of cardiac cell-based therapy

Research output: Contribution to journalReview article

27 Scopus citations

Abstract

Although the initial promise of cardiac cell-based therapy was based on the concept that stem cells engraft into diseased tissue and differentiate into beating cardiomyocytes, it is now clear that successful cell-based tissue repair involves a more complex orchestration of cellular and molecular events. Many lessons about successful tissue repair can be gleaned from the results of early-stage clinical trials. This body of work shows that cell-based therapy (with various cell sources and delivery methods) effectively prevents and reverses the remodeling process, the sine qua non of the myocardial injury reaction and anatomic substrate for subsequent clinical events. The potentially favorable remodeling responses to cell therapy have prompted a search for mechanisms of action beyond cell repopulation and guided future clinical trial design by providing more clear focus on pathophysiological endpoints signifying favorable responses to cell-based therapy. Perhaps the most important mechanistic insight is that endogenous stem/precursor cells have the potential to participate in tissue healing. With regard to the phenotype of cellular response, it is clear that parameters of remodeling, such as infarct size and ventricular dimensions, should be directly measured, thereby necessitating the use of sophisticated imaging modalities, such as cardiac magnetic resonance imaging or multidetector computed tomography. These new insights offer an optimistic outlook on the state of cell-based therapeutics for cardiac disease and suggest that pivotal clinical trials are warranted. Here, we review lessons learned from clinical trials and evaluate the choice and assessment of endpoints to best predict efficacy of cell therapy.

Original languageEnglish (US)
Pages (from-to)29-35
Number of pages7
JournalStem Cells Translational Medicine
Volume1
Issue number1
DOIs
StatePublished - Jan 1 2012

Keywords

  • Cell transplantation
  • Heart failure
  • Magnetic resonance imaging
  • Mesenchymal stem cells
  • Myocardial infarction
  • Ventricular remodeling

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Medicine(all)

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