Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium.
Under conditions of tissue injury, myocardial replication and regeneration have been reported. 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. 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.
Balsam
Leora B
LB
Departments of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California 94305, USA.
Wagers
Amy J
AJ
Christensen
Julie L
JL
Kofidis
Theo
T
Weissman
Irving L
IL
Robbins
Robert C
RC
D000818:Animals; D002454:Cell Differentiation; D002459:Cell Fusion; D019070:Cell Lineage; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D017930:Genes, Reporter / Q000235:genetics; D006098:Granulocytes / Q000166:cytology / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D012038:Regeneration