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- Title
Bone marrow-derived myocyte-like cells and regulation of repair-related cytokines after bone marrow cell transplantation
- Authors
Misao, Yu; Takemura, Genzou; Arai, Masazumi; Sato, Shigeru; Suzuki, Koji; Miyata, Shusaku; Kosai, Ken-ichiro; Minatoguchi, Shinya; Fujiwara, Takako; Fujiwara, Hisayoshi
- Abstract
Abstract: Objective: Whether bone marrow cells injected following acute myocardial infarction (MI) transdifferentiate into cardiomyocytes remains controversial, and how these cells affect repair-related cytokines is not known. Methods: Autologous bone marrow-derived mononuclear cells (BM-MNCs) labeled with DiI, 1,1′-dioctadecyl-1 to 3,3,3′,3′-tetramethylindocarbocyanine perchlorate, or saline were intravenously injected into rabbits 5 h following a 30-min ischemia and reperfusion protocol, and cardiac function and the general pathology of the infarcted heart were followed up 1 and 3 months post-MI. To search for regenerated myocardium, electron microscopy as well as confocal microscopy were performed in the infarcted myocardium 7 days post-MI. Expression levels of repair-related cytokines were evaluated by immunohistochemistry and Western blotting. Results: Improvements in cardiac function and reductions in infarct size were observed in the BM-MNC group 1 month and 3 months post-MI. Using electron microscopy 7 days after infarction, clusters of very immature (fetal) and relatively mature cardiomyocytes undergoing differentiation were identified in the infarcted anterior LV wall in the BM-MNC group, though their numbers were small. These cells contained many small and dense DiI particles (a BM-MNC marker), indicating that cardiomyocytes had regenerated from the injected BM-MNCs. The expression of both transforming growth factor-β, which stimulates collagen synthesis and matrix metalloproteinase-1, a collagenase, were both down-regulated 7 days and 1 month post-MI in the BM-MNC group. Stromal cell-derived factor-1, which is known to recruit BM-MNCs into target tissues, was overexpressed in the infarcted areas of BM-MNC hearts 7 days post-MI. Conclusions: Intravenous transplantation of BM-MNCs leads to the development of BM-MNC-derived myocyte-like cells and regulates the expression of repair-related cytokines that facilitate repair following myocardial infarction.
- Subjects
BONE marrow; IMMUNE system; REPAIRING; MEAN time to repair
- Publication
Cardiovascular Research, 2006, Vol 69, Issue 2, p476
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1016/j.cardiores.2005.11.001