Adult bone marrow stem cells regenerate myocardium in ischemic heart disease.
Recent studies have demonstrated the existence of several populations of primitive cells in mouse and human bone marrow that have the capacity, both in vitro and in vivo, to give rise to cells of all three germ layers. Mesenchymal/stromal stem cells and hematopoietic stem cells are the leading candidates for this activity that some believe may recapitulate the potential of embryonic stem cells. Very little is known about the molecular controls for this adult stem cell activity commonly referred to as transdifferentiation or plasticity. Regeneration of a large number of cell types and tissues has been investigated with one of the most extensively studied being the myocardium. These studies involved ligation of the left coronary artery in adult mice and the direct injection or mobilization of bone marrow stem cells. Using this protocol we, and others, have observed the generation of new cardiomyocytes and endothelial cells in the zone of ischemic myocardium. This approach has progressed to clinical trials at several academic institutions. Although the preliminary findings from these trials do not permit unequivocal conclusions, they do suggest that safety and feasibility are not significant problems that would argue against extending these trials in a large, randomized, double-blinded study. When considerations such as these are addressed, cell therapy may become a new modality in the treatment of heart patients.
Orlic
Donald
D
Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. dorlic@nhgri.nih.gov
D000818:Animals; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D017202:Myocardial Ischemia / Q000628:therapy*; D009206:Myocardium / Q000166:cytology* / Q000473:pathology*; D012727:Sex Characteristics