BACKGROUND Due to the low survival rate of cell transplantation, stem cell has not been widely used in clinical treatment of acute myocardial infarction (AMI). In this study, we immobilized the C domain peptide of insulin-like growth factor-1 on chitosan (CS-IGF-1C) to obtain bioactive hydrogel. The purpose was to investigate whether CS-IGF-1C hydrogel incorporated with human placenta-derived mesenchymal stem cells (hP-MSCs) can boost the survival of hP-MSCs and enhance their therapeutic effects. METHODS hP-MSCs, which continuously expressed green fluorescent protein (GFP) and firefly luciferase (Fluc), were transplanted with CS-IGF-1C hydrogel into a mouse myocardial infarction model. Cell survival was detected by bioluminescence imaging (BLI), and cardiac function was measured by echocardiogram. Real-time PCR and histological analysis were used to explore the therapeutic mechanism of CS-IGF-1C hydrogel. RESULTS CS-IGF-1C hydrogel could induce the proliferation of hP-MSCs and exert anti-apoptotic effects in vitro. The Calcine-AM/PI staining results showed that hP-MSCs seeded on CS-IGF-1C hydrogel could protect neonatal mouse ventricular cardiomyocytes (NMVCs) against oxidative stress. It was observed by BLI that CS-IGF-1C hydrogel injected into ischemic myocardium could improve the survival rate of hP-MSCs. Histology analysis indicated that co-transplantation of the CS-IGF-1C hydrogel and hP-MSCs could increase angiogenesis, reduce collagen deposition, ameliorate left ventricular expanded, and further promote the recovery of cardiac function. Besides, we found that the inflammatory response was inhibited and the expression of apoptosis-related genes was downregulated by CS-IGF-1C hydrogel. CONCLUSIONS CS-IGF-1C hydrogel provides a conducive microenvironment for cells and significantly boosts the survival of hP-MSCs in mouse myocardial infarction model, which suggest that it may be a potential candidate for prolonging the therapeutic effect of hP-MSCs during AMI.

中文翻译：

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IGF-1C结构域修饰的水凝胶增强了干细胞治疗AMI的功效。

背景技术由于细胞移植的存活率低，干细胞尚未广泛用于急性心肌梗塞（AMI）的临床治疗中。在这项研究中，我们将胰岛素样生长因子1的C结构域肽固定在壳聚糖上（CS-IGF-1C），以获得生物活性水凝胶。目的是研究将CS-IGF-1C水凝胶与人胎盘来源的间充质干细胞（hP-MSCs）掺入能否提高hP-MSC的存活率并增强其治疗效果。方法将连续表达绿色荧光蛋白（GFP）和萤火虫荧光素酶（Fluc）的hP-MSCs与CS-IGF-1C水凝胶一起移植到小鼠心肌梗死模型中。通过生物发光成像（BLI）检测细胞存活，并通过超声心动图测量心脏功能。通过实时荧光定量PCR和组织学分析探讨CS-IGF-1C水凝胶的治疗机制。结果CS-IGF-1C水凝胶可诱导hP-MSCs增殖，并在体外发挥抗凋亡作用。Calcine-AM / PI染色结果表明，接种在CS-IGF-1C水凝胶上的hP-MSC可以保护新生小鼠心室心肌细胞（NMVC）免受氧化应激。通过BLI观察到，将CS-IGF-1C水凝胶注入缺血心肌可以提高hP-MSC的存活率。组织学分析表明，CS-IGF-1C水凝胶与hP-MSCs共同移植可增加血管生成，减少胶原蛋白沉积，改善左心室扩张，并进一步促进心脏功能的恢复。除了，我们发现，CS-IGF-1C水凝胶抑制了炎症反应，并下调了凋亡相关基因的表达。结论CS-IGF-1C水凝胶为细胞提供了有利的微环境，并显着提高了hP-MSC在小鼠心肌梗死模型中的存活率，这表明它可能是延长AMI期间hP-MSCs治疗效果的潜在候选者。