Gelatin Hydrogel Enhances the Engraftment of Transplanted Cardiomyocytes and Angiogenesis to Ameliorate Cardiac Function after Myocardial Infarction.
Gelatin Hydrogel Enhances the Engraftment of Transplanted Cardiomyocytes and Angiogenesis to Ameliorate Cardiac Function after Myocardial Infarction.
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DOI：
10.1371/journal.pone.0133308
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Fukuda K
中科院分区：
文献类型：
--
作者：
Nakajima K;Fujita J;Matsui M;Tohyama S;Tamura N;Kanazawa H;Seki T;Kishino Y;Hirano A;Okada M;Tabei R;Sano M;Goto S;Tabata Y;Fukuda K
细胞移植治疗将是解决心脏移植供体短缺的突破口。然而，心肌细胞（CM）移植在恢复心肌梗死（MI）后的心脏功能方面相对低效，因为移植CM的植入率低。为了改善CM的植入，必须发明新的移植策略。明胶水凝胶（GH）是一种可生物降解的水溶性高分子凝胶。明胶是由胶原蛋白制成的。虽然我们观察到胶原蛋白强烈诱导血小板聚集，可能导致冠状动脉微栓塞，GH没有增强血栓形成。因此，GH是心力衰竭后细胞治疗的合适生物材料。为观察生长激素（GH）对心功能的改善作用，将5×106或1 × 106个CM细胞与GH（10 mg/ml）一起移植到大鼠心肌梗死区。我们将该组与假手术大鼠、磷酸盐缓冲盐水（PBS）中的CM、仅PBS和仅GH移植组进行比较。移植后3周，通过超声心动图评估心脏功能。超声心动图证实，与CM+PBS组（75.1±3.4% vs. 60.7± 5.9%，p<0.05）、仅PBS组和仅GH组（60.1± 6.5%，65.0± 2.8%，p<0.05）相比，移植5×106 CM + GH显著改善心脏收缩功能。病理学分析表明，CM+GH组中，CM在梗死心肌中有效地植入（p<0.01），并且在瘢痕的中心和周边区域的血管生成显著增强（p<0.05）。此外，定量RT-PCR显示，CM+GH组中血管生成细胞因子，如碱性成纤维细胞生长因子、血管内皮生长因子和肝细胞生长因子显著富集（p<0.05）。在这里，我们报告说，生长激素限制CM有效地在梗死心肌移植后，和CM移植生长激素改善心脏功能的直接收缩作用和增强血管生成。
Cell transplantation therapy will mean a breakthrough in resolving the donor shortage in cardiac transplantation. Cardiomyocyte (CM) transplantation, however, has been relatively inefficient in restoring cardiac function after myocardial infarction (MI) due to low engraftment of transplanted CM. In order to ameliorate engraftment of CM, the novel transplantation strategy must be invented. Gelatin hydrogel (GH) is a biodegradable water-soluble polymer gel. Gelatin is made of collagen. Although we observed that collagen strongly induced the aggregation of platelets to potentially cause coronary microembolization, GH did not enhance thrombogenicity. Therefore, GH is a suitable biomaterial in the cell therapy after heart failure. To assess the effect of GH on the improvement of cardiac function, fetal rat CM (5×106 or 1x106 cells) were transplanted with GH (10 mg/ml) to infarcted hearts. We compared this group with sham operated rats, CM in phosphate buffered saline (PBS), only PBS, and only GH-transplanted groups. Three weeks after transplantation, cardiac function was evaluated by echocardiography. The echocardiography confirmed that transplantation of 5×106 CM with GH significantly improved cardiac systolic function, compared with the CM+PBS group (fractional area change: 75.1±3.4% vs. 60.7±5.9%, p<0.05), only PBS, and only GH groups (60.1±6.5%, 65.0±2.8%, p<0.05). Pathological analyses demonstrated that in the CM+GH group, CM were efficiently engrafted in infarcted myocardium (p<0.01) and angiogenesis was significantly enhanced (p<0.05) in both central and peripheral areas of the scar. Moreover, quantitative RT-PCR revealed that angiogenic cytokines, such as basic fibroblast growth factor, vascular endothelial growth factor, and hepatocyte growth factor, were significantly enriched in the CM+GH group (p<0.05). Here, we report that GH confined the CM effectively in infarcted myocardium after transplantation, and that CM transplanted with GH improved cardiac function with a direct contraction effect and enhanced angiogenesis.