Stem cell therapy for ischemic heart disease: Where are we?

PURPOSE OF REVIEW: Stem cell transplantation is currently generating a great deal of interest in the treatment of ischemic heart disease (IHD) as the replacement of akinetic scar tissue by viable myocardium should improve cardiac function, impede progressive left ventricular remodeling, and revascularize ischemic areas. Substantial work in stem cell therapy for ischemic heart disease has recently been reported. RECENT FINDINGS: Stem cell populations have been expanding. Most recently, induced pluripotent stem (iPS) cells have been discovered that have the potential to revolutionize stem cell therapy. Many of the efforts in stem cell therapy for ischemic heart disease have been inconclusive and often contradicting. Transdifferentiation of stem cells into cardiomyocytes remains controversial. The therapeutic effect of the stem cell seems consistent with paracrine function rather than transdifferentiation. Systemic and micromilieu factors appear to dictate the fate of implanted stem cells. SUMMARY: Although animal studies produce controversial results, and many basic questions remain unanswered, more and more clinical trials are underway. Consequently, researchers must begin to focus upon a few basic critical issues: the modulation of the systemic and microenvironment for stem cells in order to augment stem cell survival and transdifferentiation; the underlying mechanisms of stem cell therapy and the fate of stem cells; differentiation into myocytes or other terminal cell populations with favorable paracrine functions.