Abstract 911: Kit-Positive Cardiac Stem Cells (CSCs) Can Be Generated in Damaged Heart from Bone Marrow-Derived Cells
Introduction: The origin(s) of adult CSCs, is presently unknown. The expression of Kit (a marker of several stem cell types, including hematopoietic stem cells), suggests that Kitpos CSCs may derive, at least in part, from extracardiac sources. In addition, following myocardial infarction, bone marrow (BM) cells may be mobilized, home into the heart and trans-differentiate into cardiomyocytes.
Can BM generate Kitpos CSCs, at least in response to heart damage?
Conversely, can CSCs contribute to bone marrow reconstitution following myeloablation?
Methods and Results: To study the contribution of the BM to the origin of Kitpos CSCs we transplanted lethally-irradiated mice with bone marrow (BM) cells expressing GFP under the control of mouse kit regulatory DNA regions. After 4 months the transplanted mice were infarcted by LAD ligation, and then sacrificed after 2–3 additional weeks. We isolated the CSCs from the heart of the transplanted-infarcted and non infarcted mice and expanded them in vitro as cardiospheres (CSs), according to our previously described culture system. All the CSs derived from the infarcted hearts were GFP-positive; conversely few if any CSs cuold be obtained from the non infarcted mice and those were GFPneg. This result was confirmed by PCR analysis of genomic DNA of individual CSs. GFP-positive-CSs express cardiac differentiation markers both spontaneously and when co-cultured with neonatal mouse cardiomyocytes. Confocal analysis has demonstrated that GFP-positive-CSs express cardiac specific markers (TnI, MHC, Cx-43, Nkx2.5) mainly in the external layers. To test whether cardiospheres (harboring Kitpos cells) are capable of long term hematopoietic reconstitution, we transplanted dissociated CSs into lethally irradiated mice. Analysis of the recipient animals did not show any CSCs-derived bone marrow cell.
At least in pathological conditions, part of the kitpos CSCs population may derive from cells that originate in the BM and are able to adopt in the heart the same functions and features of local CSCs.
At least in our conditions bone marrow cells derived from CSCs could not be demonstrated, suggesting that CSCs may not be able to adopt a hematopoietic cell fate.