Construction of a vascularized hydrogel for cardiac tissue formation in a porcine model
Construction of a vascularized hydrogel for cardiac tissue formation in a porcine model
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DOI：
10.1002/term.2634
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发表时间：
2018-04-01
影响因子：
3.3
通讯作者：
Shim, Winston
中科院分区：
文献类型：
--
作者：
Ja, K. P. Myu Mai;Lim, Kee Pah;Shim, Winston
替换心肌梗死丢失的心脏组织仍然是再生治疗恢复心脏功能的治疗目标。我们评估了使用多能干细胞衍生的心肌细胞或对照成纤维细胞灌注纤维蛋白/胶原水凝胶构建大型人类心脏组织构建体的可行性，并在猪模型的外周血管系统中进行异位植入3周。最后，将一个优化的血管化心脏结构移植到猪心肌上，持续2周。心肌移植的人心脏结构显示出新生的组织样组织，在重塑的胶原基质内具有对齐的心肌细胞。然而，在心肌移植结构中没有观察到结构内心肌细胞密度的显著变化（人胚胎干细胞[hESC]衍生的心肌细胞[n=4]：70.5 +/- 22.8肌钙蛋白I+心肌细胞/高倍视野[HPF]）与外周植入构建体相比（hESC衍生的心肌细胞[n=4]：59.0 +/-19.6肌钙蛋白I+心肌细胞/HPF;人诱导多能干细胞衍生的心肌细胞[n=3]：50.9 +/-8.5肌钙蛋白I+心肌细胞/HPF，p=ns）。然而，心肌移植结构显示新生血管增加（194.4 ± 24.7微血管/mm 2组织，p
Replacing cardiac tissues lost to myocardial infarction remains a therapeutic goal for regenerative therapy in recovering cardiac function. We assessed the feasibility of constructing a macrosized human cardiac tissue construct using pluripotent stem cell-derived cardiomyocytes or control fibroblasts infused fibrin/collagen hydrogel and performed ectopic implantation in peripheral vascular system of a porcine model for 3weeks. Finally, an optimized vascularized cardiac construct was explanted and grafted onto porcine myocardium for 2weeks. Myocardial-grafted human cardiac constructs showed a nascent tissue-like organization with aligned cardiomyocytes within the remodelled collagen matrix. Nevertheless, no significant changes in intraconstruct density of cardiomyocytes were observed in the myocardial-grafted constructs (human embryonic stem cell [hESC]-derived cardiomyocyte [n=4]: 70.5 +/- 22.8 troponin I+ cardiomyocytes/high power field [HPF]) as compared to peripherally implanted constructs (hESC-derived cardiomyocyte [n=4]: 59.0 +/- 19.6 troponin I+ cardiomyocytes/HPF; human induced pluripotent stem cell-derived cardiomyocyte [n=3]: 50.9 +/- 8.5 troponin I+ cardiomyocytes/HPF, p=ns). However, the myocardial-grafted constructs showed an increased in neovascularization (194.4 +/- 24.7 microvessels/mm(2) tissue, p