Endogenous bone-marrow-derived stem cells contribute only a small proportion of regenerated myocardium in the acute infarction model.
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.
Fukuhara
Shinya
S
Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center, Osaka, 565-8565, Japan.
Tomita
Shinji
S
Nakatani
Takeshi
T
Yutani
Chikao
C
Kitamura
Soichiro
S
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000378:metabolism / Q000494:pharmacology; D007381:Intermediate Filament Proteins / Q000378:metabolism; D049408:Luminescent Agents / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D012038:Regeneration; D019210:Troponin I / Q000378:metabolism
D007381:Intermediate Filament Proteins; D049408:Luminescent Agents; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D019210:Troponin I; D049452:Green Fluorescent Proteins