Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium

Abstract

Under conditions of tissue injury, myocardial replication and regeneration have been reported¹. A growing number of investigators have implicated adult bone marrow (BM) in this process, suggesting that marrow serves as a reservoir for cardiac precursor cells^2,3,4,5,6. It remains unclear which BM cell(s) can contribute to myocardium, and whether they do so by transdifferentiation or cell fusion. Here, we studied the ability of c-kit-enriched BM cells, Lin^- c-kit⁺ BM cells and c-kit⁺ Thy1.1^lo Lin^- Sca-1⁺ long-term reconstituting haematopoietic stem cells to regenerate myocardium in an infarct model. Cells were isolated from transgenic mice expressing green fluorescent protein (GFP) and injected directly into ischaemic myocardium of wild-type mice. Abundant GFP⁺ cells were detected in the myocardium after 10 days, but by 30 days, few cells were detectable. These GFP⁺ cells did not express cardiac tissue-specific markers, but rather, most of them expressed the haematopoietic marker CD45 and myeloid marker Gr-1. We also studied the role of circulating cells in the repair of ischaemic myocardium using GFP⁺–GFP^- parabiotic mice. Again, we found no evidence of myocardial regeneration from blood-borne partner-derived cells. Our data suggest that even in the microenvironment of the injured heart, c-kit-enriched BM cells, Lin^- c-kit⁺ BM cells and c-kit⁺ Thy1.1^lo Lin^- Sca-1⁺ long-term reconstituting haematopoietic stem cells adopt only traditional haematopoietic fates.