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Transplantation of adipose tissue-derived stromal cells attenuates ventricular remodeling and improves ventricular function in a rat model of myocardial infarction.
충북대학교 의과대학 내과학교실
박노관, 황경국, 심태진, 최은주, 박건재, 배장환, 김동운, 조명찬.
Backgrounds and Objectives; Most studies of cellular cardiomyoplasty were focused on bone marrow-derived mesenchymal stem cells (BM-MSCs) and endothelial progenitor cells. Compared to BM-MSCs, adipose tissue derived stromal cells (ADSCs) can be easily harvested from patients by a minimal invasive method and also easily cultured. We investigated the effects of direct transplantation of rat ADSCs on the ventricular remodeling and its function in a rat model of myocardial infarction (MI). Methods; Rat ADSCs (rADSCs) were cultured from abdominal adipose tissue of Sprague-Dawley rats. In-vitro, to evaluate the differentiation of rADSCs into cardiomyocyes (CMCs), DAPI-labeled rADSCs (1ⅹ105 cells) were co-cultured with neonatal rat cardiomyocytes (rCMCs, 4ⅹ105 cells) for 10 days. Expression of troponin-I (Tn-I) and myosin heavy chain (MHC) were evaluated by confocal laser microscope. In-vivo, DAPI-labeled rADSC (1ⅹ106 cells, rADSC group, n=3) or Dulbecco's modified Eagle medium (control group, n=3) were directly injected at the ischemic border-zone at post-MI 1 week. MI was induced by permanent ligature of left anterior descending artery. At 4 weeks after transplantation, echocardiographic and histological analyses were evaluated. Results; rADSCs expressed CD13, CD34 and CD90 but not CD 31 and CD 45. In-vitro, DAPI(+)/Tn-I(+) and DAPI(+)/MHC(+) cells were observed by confocal laser microscope. In-vivo, rADSCs were survived up to 4 weeks after transplantation in border-zone of MI. DAPI(+)/Tn-I(+) cells were observed. Compared to control, left ventricular size was significantly decreased and fraction shortening was siginicantly increased (9.5±0.1 vs 8.5±2.2 mm, 15.4±10.0 vs 29.2±13.9 %, respectively). Summaries and Conclusion; rADSC showed the expression of cardiac specific proteins under the co-culture with rCMCs. And, transplanted rADSCs were survived up to 4 weeks and attenuated post-MI ventricular remodeling. Taken together, these findings suggest that rADSCs has considering potential for cellular cardiomyoplasty.


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