Are resident c-Kit+ cardiac stem cells really all that are needed to mend a broken heart?

The ability of the heart to regenerate through new myocyte formation is a subject of intense investigation. Here we will discuss a provocative new publication from Nadal-Ginard and Torella and colleagues where they report that c-kit resident cardiac stem cells are necessary and sufficient to explain cardiac regeneration fully. Nadal-Ginard and Torella and colleagues have provided yet another exciting installment in the evolving cardiac regeneration and stem cell saga. The ongoing debate centers on if and how the normal adult mammalian heart renews its myocyte pool and if and how new myocytes are generated when diseases induce myocyte death. Their recently published article1 provides supportive evidence that c-kit-marked resident cardiac stem cells (CSCs) are both necessary and sufficient for cardiac regeneration, and that the differentiation of CSCs into cardiac myocytes constitutes the primary mechanism for cellular replacement following diffuse, isoproterenol (ISO)-induced injury to the heart. Although many of the approaches and conclusions put forth are already represented in the literature, the unique aspects of this report are the injury model used as well as the simply overwhelming amount of supportive experimentation presented. However, as in any provocative ongoing scientific saga, new results engender skepticism and lead to new questions that can only be answered by additional studies from other groups. In the recent past, 2 diametrically opposed views have emerged as to whether the heart regenerates after cardiac injury by forming new myocytes. One group2–6 has presented strong data that the heart is a highly malleable organ that is capable of near-complete regeneration, although the cell source responsible for this regenerative potential varies from the myocytes themselves, to c-kit-positive bone marrow cells, c-kit-positive resident CSCs, cardiospheres, resident fibroblasts, or tissue residence mesenchymal stem cells of various markers. The other group,6–8 with polar opposite …