Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium

Abstract

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.

Adult bone marrow–derived stem cells for organ regeneration and repair

“…It was based on the assumption that transplantation of stem cells capable of parenchymal differentiation are able to replace dead cells in damaged tissues, thereby repairing a critically injured organ. Although this repair process might be true in certain model systems, even if accomplished by cell fusion (Masson et al, 2004), it is a very rare and slow process, thereby rendering it probably not effective in injuries with rapid pathophysiological kinetics such as acute myocardial injury (Balsam et al, 2004 …”

Overview of recent advances in molecular cardiology

“…Pluripotent stem cells are cells that have not taken on the identity of any specific cell type and are not yet committed to any dedicated function; they can divide indefinitely and may be induced to give rise to one or more specialized cell types. Murry et al (50) and Balsam et al (51) recently reported that hematopoietic stem cells failed to transdifferentiate into cardiac myocytes in myocardial infarcts. The stem cells, however, developed into different blood cell types, despite being in the heart.…”

Medicina regenerativa con células madre adultas

“…De forma natural se ha podido observar que tras un IAM se produce una movilización de células madre (CD34+) desde la médula ósea a la circulación periférica, con posterior localización en el miocardio dañado 2,3 , aunque dicha movilización es mínima e insuficiente para regenerar la totalidad del tejido necrosado. Sin embargo, la trasdiferenciación en el caso de las células hematopoyéticas no ha sido observada por todos los autores y existen resultados discordantes [4][5][6] . Asimismo, parece que la transformación hacia miocitos es debida en parte a un fenómeno de fusión celular que acompañaría al fenómeno de transdiferenciación celular 7 .…”