Generation and Stem Cell Repair of Cardiac Tissue

Abstract

Cellular-based therapies may be a future strategy for treatment of cardiac injury. Full differentiation of the heart leaves an organ without a stem cell population to respond to injury. This can be addressed by providing cardiomyocyte precursors from embryonic or adult stem cells. The coronary vasculature derives from both vasculogenesis from the putative hemangioblast and angiogenesis by sprouting from newly formed vessels from the proepicardium, which is formed from villi-like protrusions of the fetal liver. Interruption of the vascular supply leads to infarction of myocardium and death of myocardiocytes. Normally there is little or no regeneration of this tissue, which heals by the process of inflammation and scarring. Although some myocardiocytes may proliferate after injury, these represent <0.01% and are insufficient to mediate any useful replacement. The endothelial cells of the coronary arteries are able to proliferate in response to the inflammation following an infarct and establish a collateral circulation to support the remaining heart and scar tissue. Cell transplantation experiments have explored the use of cardiomyocytes derived from embryonic stem cells or fetal hearts for cardiac repair with mixed success. Adult muscle stem cells (satellite cells) may populate ischemic heart tissue and potentially improve function, but they do not establish electromechanical coupling with cardiac myocytes. Mesenchymal stem cells (MSCs) from the bone marrow differentiate into multiple cell types in vitro including myocardial-like cells, which may contract in vitro. These cells can also be grafted onto ischemic heart tissue, but their degree of functional integration is not yet clear. Bone marrow—derived cells can be found in small numbers in recipient hearts after transient cardiac ischemia, either after bone marrow replacement of depleted mice or following direct injection into areas adjacent to the injured myocardium. Cytokines, which liberate autogenous bone marrow stem cells, may improve the outcome of experimental cardiac injury. Both bone marrow and MSCs may contribute to revascularization after injury. In selected models, transplanted stem cells may replace or restore lost gene function in the heart, and bone marrow progeny have been identified in the hearts of humans with heart transplants. Adult stem cells may be expected to play an increasing role in the treatment of many forms of heart disease, but extensive validation and development research still needs to be undertaken.