Phenotypic modulation and turnover of bone marrow-derived cells after myocardial infarction in rats.
BACKGROUND
Bone marrow-derived cells (BMCs) are critically involved in inflammation and regeneration after myocardial infarction (MI). However, the participation of BMCs in the reconstruction of infarcted myocardium remains unclear. In this study, we investigated phenotypic modulation of BMCs and their turnover in the heart following MI.


RESULTS
MI was produced in rats with intra-bone marrow-bone marrow transplantation from the syngenic rats expressing green fluorescence protein (GFP). The number of GFP-positive BMCs recruited to the infarcted myocardium peaked at 3 days after MI, and the majority of BMCs recruited to the heart after MI underwent turnover within 2 weeks. This turnover rate was unchanged for up to 16 weeks after MI, although the number of BMCs recruited to the infarcted myocardium rapidly decreased between 2 and 8 weeks after MI. A small number of BMCs recruited to the heart were positive for CD31 and α-smooth muscle actin, and the majority of these were positive for vimentin at 3 days and 4 weeks after MI. None of BMCs expressed α-actinin or von Willebrand factor 4 weeks after MI.


CONCLUSIONS
These results suggest that BMCs recruited to the heart underwent phenotypic modulation to a fibroblastic cell type and turnover within 2 weeks after MI without differentiating into cardiomyocytes or endothelial cells, and that although the number of BMCs in the infarcted myocardium decreased over time, the rate of turnover remained relatively constant during the chronic phase of MI.
Second Department of Internal Medicine, Kansai Medical University, Moriguchi City, Japan.
Daisuke
D
Sato
Hajime
H
Otani
Chiharu
C
Enoki
Masanori
M
Fujita
Naoki
N
Minato
Toshiji
T
Iwasaka
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002465:Cell Movement; D058948:Cell Tracking / Q000379:methods; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012038:Regeneration; D013997:Time Factors
D015415:Biomarkers; D049452:Green Fluorescent Proteins