Endogenous bone-marrow-derived stem cells contribute only a small proportion of regenerated myocardium in the acute infarction model

Abstract

Background: Our recent study showed that granulocyte-colony stimulating factor (G-CSF) promoted bone-marrow cells (BMC) to migrate into the infarcted heart and that they differentiated into cardiomyocytes. However, we still do not know to what degree bone-marrow-derived cardiomyocytes contribute to myocardial regeneration after injury. In this study, we verified the proportional contribution of cells from bone marrow (BM) and from non-bone marrow (n-BM) in regenerating neomyocardium after myocardial infarction.

Methods: Eight C57BL/6 mice were irradiated (900 cGy), and green fluorescent protein (GFP) mouse-derived BMCs (GFP-BMC, 1 x 10(6) cells) were injected. Four weeks later, the left descending coronary artery was ligated. Recombinant human G-CSF (200 microg/kg/day, 8 days) was injected. At 4 weeks after ligation, hearts were fixed for histology. We calculated the proportions of cardiomyocytes derived from BM and n-BM after taking the chimeric rate into consideration.

Results: The chimeric rate was 54.6% +/- 5.9%. At the infarcted border area, the total cell number was 1000.3 +/- 56.5/mm(2), and mobilized BM-derived GFP-BMC was 103.3 +/- 13.1/mm(2). After compensation with the chimeric rate, we found BM-derived troponin I-positive cells at 23.9 +/- 4.1/mm(2), nestin-positive cells at 12.9 +/- 2.6/mm(2), and Ki67-positive cells at 18.3 +/- 2.6/mm(2), respectively. We found significant differences in the contribution of troponin I-(6.7% +/- 1.7% vs 93.3% +/- 1.7%), nestin- (2.4 +/- 0.5 vs 97.6 +/- 0.5), and Ki67-positive (3.9 +/- 1.0 vs 96.1 +/- 1.0) cells derived from BM and n-BM.

Conclusions: Bone marrow was one of the origins of regenerated cardiomyocytes; however, the contribution of cells from BM was very small compared with those of n-BM origin in the infarction model.