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 cells2,3,4,5,6. 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+ Thy1.1lo 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+ Thy1.1lo Lin- Sca-1+ long-term reconstituting haematopoietic stem cells adopt only traditional haematopoietic fates.
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We thank G. Hoyt for technical assistance with animal surgery, and V. Mariano and L. Hildalgo for animal care. This work was supported by the Falk Cardiovascular research fund (R.C.R.) and an NIH grant (I.L.W.). L.B.B. was supported by Thoracic Surgery Foundation Nina Starr Braunwald Research Training Fellowship; A.J.W. was supported by an American Cancer Society grant and the Frederick Frank/Lehman Brothers, Inc. Irvington Institute Fellowship; J.L.C. was supported by a NIH Training Grant in Molecular and Cellular Immunobiology; and T.K. was supported by a German Research Society Training Grant.
Table 1: Echocardiographic function of cell-treated vs. saline-treated infarcted hearts at 2 weeks and 6 weeks post-injury; Table 2: Hemodynamic parameters of cell-treated and saline-treated infarcted animals 6 weeks after infarction; Table 3: Hematopoietic chimerism in parabiotic pairs.
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SDF 1-alpha Attenuates Myocardial Injury Without Altering the Direct Contribution of Circulating Cells
Journal of Cardiovascular Translational Research (2018)