Bone Marrow-Derived Cells Regenerate Kit+ Cardiac Stem Cells (CSCs) in Damaged Heart.

A growing amount of data indicates that the heart harbours stem cells (CSCs) with regenerative potential, however the origin(s) of adult CSCs is still unknown. The expression of Kit a marker of several stem cell types, including hematopoietic and cardiac stem cells, suggests that Kit positive-CSCs may derive, at least in part, from extracardiac sources. In addition, it has been suggested that bone marrow (BM) cells may be mobilized, home into the heart and trans-differentiate into cardiomyocytes, following myocardial infarction. To investigate whether BM cells can contribute to repopulate the cardiac Kit+ stem cell pool, we transplanted BM cells from a mouse line expressing transgenic Green Fluorescent Protein (GFP) under the control of Kit regulatory elements, into wild type irradiated recipients. After hematological reconstution (4–5 months) and following cardiac infarction, cardiac cells were grown in vitro into typical “cardiospheres” (Messina et al., Circ. Res. 95,911;2004). The cardiospheres obtained, although not numerous, were all GFP fluorescent; this result was confirmed by PCR analysis of genomic DNA of individual CSs. At confocal microscopy, cells at the periphery of CSs showed coexistence of low GFP with cardiac markers, such as Troponin I and the transcription factor NKx2.5, consistent with the expected kit downregulation during cardiac differentiation. Our results show that cells of bone marrow origin can give rise, after homing into the heart, to cells with properties of Kit+ CSC. In contrast, CSCs isolated from kit/GFP transgenic mice are not able, upon transplantation, to repopulate the bone marrow of wild-type irradiated recipients. Thus, at least in pathological conditions, part of the Kit-positive CSCs population may be generated by BM-derived cells, capable of adopting in the heart the same function and features of cardiac stem cells.