1 Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan. 2 Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute. 3 Department of Neuropharmacology, Faculty of Pharmaceutical Science, Fukuoka University, Fukuoka, Japan. 4 National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan. 5 Department of Perinatology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan. 6 Department of Obstetrics and Gynecology, Mie University School of Medicine, Mie, Japan. 7 Address correspondence to: Hiroshi Hosoda, M.D., Ph.D., Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Transplantation. 2013 Oct 27;96(8):697-706. doi: 10.1097/TP.0b013e31829f753d.
BACKGROUND: Mesenchymal stem cell (MSC) transplantation has been pursued as a new method to repair damaged myocardium. We focused on the fetal membrane (FM) as an alternative source to bone marrow (BM)-derived MSCs. In this study, we investigated whether transplantation of allogeneic FM-MSC sheets could attenuate myocardial dysfunction in a rat chronic myocardial infarction (MI) model. METHODS: Sheets of allogeneic FM-MSC or autologous BM-MSC were transplanted into the scarred myocardium 4 weeks after coronary ligation. RESULTS: Four weeks after transplantation, both allogeneic FM-MSC and autologous BM-MSC sheets had significantly improved cardiac function and reduced myocardial fibrosis compared with the untreated MI group. In both MSC sheet-transplanted groups, the peri-infarct regional capillary density was increased. Some engrafted MSCs formed vascular structures and were positive for lectin I and α-smooth muscle actin. The numbers of engrafted cells and differentiated cells were very low after both types of MSC sheet transplantation. CD3 T cells did not increase in the transplantation site, but CD163 M2 macrophages increased in the groups transplanted with allogeneic FM-MSC and autologous BM-MSC. CONCLUSIONS: Transplantation of allogeneic FM-MSC or autologous BM-MSC sheets attenuated myocardial dysfunction in a rat MI model to a similar degree. The engraftment rate of transplanted cells and immune cell infiltration into the transplanted area did not differ between the two types of MSC transplants. M2 macrophage induction has possible involvement in the therapeutic effects of MSC transplantation. Allogeneic FM-MSC sheet transplantation might be a new therapeutic strategy after MI.
背景：间充质干细胞（MSC）移植已被作为一种修复受损心肌的新方法进行研究。我们专注于胎膜（FM）作为骨髓（BM）衍生 MSC 的替代来源。在这项研究中，我们研究了同种异体 FM-MSC 片是否可以减轻大鼠慢性心肌梗死（MI）模型中的心肌功能障碍。 方法：在冠状动脉结扎后 4 周，将同种异体 FM-MSC 或自体 BM-MSC 片移植到瘢痕心肌中。 结果：移植 4 周后，与未治疗的 MI 组相比，同种异体 FM-MSC 和自体 BM-MSC 片均显著改善了心脏功能并减少了心肌纤维化。在两种 MSC 片移植组中，梗死周边区域的毛细血管密度均增加。一些植入的 MSC 形成了血管结构，并对凝集素 I 和α-平滑肌肌动蛋白呈阳性。两种类型的 MSC 片移植后，植入细胞和分化细胞的数量都非常低。移植部位的 CD3 T 细胞没有增加，但同种异体 FM-MSC 和自体 BM-MSC 移植组的 CD163 M2 巨噬细胞增加。 结论：同种异体 FM-MSC 或自体 BM-MSC 片移植均可在一定程度上减轻大鼠 MI 模型的心肌功能障碍。两种类型的 MSC 移植中，移植细胞的植入率和免疫细胞浸润到移植区域没有差异。M2 巨噬细胞的诱导可能参与了 MSC 移植的治疗效果。同种异体 FM-MSC 片移植可能是 MI 后的一种新的治疗策略。
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