Basic Science
The lack of appropriate regenerative capacity of the heart has been the spur to early clinical trials using autologous stem cells (bone marrow-derived and skeletal myoblast) for cardiac repair. Associated in vivo and in vitro laboratory experiments have been essential in advancing understanding of mechanism of benefit or harm from these cells, and in suggesting other sources of stem cells for cardiac application. Skeletal myoblasts have dangers, in that lack of integration with myocardium produces an arrhythmic substrate. Bone marrow-derived stem cells, while safer, do not generate significant new cardiac muscle as part of their beneficial actions, suggesting an angiogenic mechanism or paracrine protection of existing cardiomyocytes. Other adult stem cells, primarily from heart but also from organs such as testis, are currently being characterised as source of new cardiac tissue. Embryonic stem cells reliably produce contracting cardiac muscle, and are a likely candidate for future repair when problems of teratoma formation and immune response have been solved. They are also more suited to tissue engineering application, because of their ready availability and potential for expansion. Study of the biology of stem cells is also generating new paradigms for understanding the intrinsic regenerative capacity of the heart.