Department of Anatomy and Histology and Embryology, Shanghai Medical School of Fudan University, China.
Biochem Biophys Res Commun. 2010 Aug 13;399(1):42-8. doi: 10.1016/j.bbrc.2010.07.031. Epub 2010 Jul 15.
Progress in stem cell transplantation for the treatment of myocardial infarction is hampered by the poor retention and survival of the implanted cells. To enhance cell survival and differentiation and thereby improve the efficiency of stem cell therapy, we constructed a novel self-assembling peptide by attaching an RGDSP cell-adhesion motif to the self-assembling peptide RADA16. c-kit(pos)/Nkx2.5(low)/GATA4(low) marrow-derived cardiac stem cells (MCSCs), which have a specific potential to differentiate into cardiomyocytes, were isolated from rat bone marrow. The cytoprotective effects of RGDSP scaffolds were assessed by exposure of MCSCs to anoxia in vitro. The efficacy of transplanting MCSCs in RGDSP scaffolds was evaluated in a female rat MI model. The designer self-assembling peptide self-assembled into RGDSP nanofiber scaffolds under physiological conditions. RGDSP scaffolds were beneficial for the growth of MCSCs and protected them from apoptosis and necrosis caused by anoxia. In a rat MI model, cardiac function was improved and collagen deposition was markedly reduced in the group receiving MCSCs in RGDSP scaffolds compared with groups receiving MCSCs alone, RGDSP scaffolds alone or MCSCs in RADA16 scaffolds. There were more surviving MCSCs in the group receiving MCSCs in RGDSP scaffolds than in the groups receiving MCSCs alone or MCSCs in RADA16 scaffolds. Most of the Y chromosome-positive cells expressed cardiac troponin T and connexin43 (Cx-43). These results suggest that RGDSP scaffolds provide a suitable microenvironment for the survival and differentiation of MCSCs. RGDSP scaffolds enhanced the efficacy of MCSC transplantation to repair myocardium and improve cardiac function.
干细胞移植治疗心肌梗死的进展受到植入细胞保留和存活不良的阻碍。为了提高细胞存活率和分化能力，从而提高干细胞治疗的效率，我们通过将 RGDSP 细胞黏附基序连接到自组装肽 RADA16 上来构建了一种新型的自组装肽。c-kit(pos)/Nkx2.5(low)/GATA4(low)骨髓源性心肌干细胞（MCSCs）具有特异地分化为心肌细胞的潜能，从大鼠骨髓中分离出来。通过体外使 MCSCs 缺氧来评估 RGDSP 支架的细胞保护作用。在雌性大鼠 MI 模型中评估了将 MCSCs 移植到 RGDSP 支架中的效果。设计的自组装肽在生理条件下自组装成 RGDSP 纳米纤维支架。RGDSP 支架有利于 MCSCs 的生长，并保护它们免受缺氧引起的凋亡和坏死。在大鼠 MI 模型中，与单独接受 MCSCs、单独接受 RGDSP 支架或接受 MCSCs 在 RADA16 支架中的大鼠相比，接受 MCSCs 在 RGDSP 支架中的大鼠心功能得到改善，胶原沉积明显减少。与单独接受 MCSCs 或接受 MCSCs 在 RADA16 支架中的大鼠相比，接受 MCSCs 在 RGDSP 支架中的大鼠中存活的 MCSCs 更多。大多数 Y 染色体阳性细胞表达心肌肌钙蛋白 T 和连接蛋白 43（Cx-43）。这些结果表明，RGDSP 支架为 MCSCs 的存活和分化提供了合适的微环境。RGDSP 支架增强了 MCSC 移植修复心肌和改善心功能的效果。
