【科技前瞻】Biomater Sci：间充质干细胞外泌体可促进心脏修复

生物_医药_科研 2019-08-05

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干细胞来源的外泌体是心血管疾病的潜在疗法，然而体内移植后外泌体的低保留率仍然是临床应用中的主要挑战。近期研究人员利用功能性多肽水凝胶包封人脐带间充质干细胞来源的外泌体，增加了外泌体在体内的保留率和稳定性，达到了改善心肌梗塞大鼠的心脏功能。相关研究结果发表在Biomaterials Science杂志上。

缺血性心脏病（Ischemic heart diseases）是世界范围内疾病死亡的主要原因之一。由于成人心肌细胞属于非增殖性质的终末分化细胞，不会发生有丝分裂，受损的心肌通常被纤维化的瘢痕组织取代，最终会导致心力衰竭。与干细胞相比，外泌体表现出与其来源细胞类似的有益效果。重要的是，外泌体不会引发宿主的免疫反应，从而避免与干细胞移植相关的免疫排斥风险。然而基于外泌体的治疗目前存在着一些困难，比如，注射到体内的外泌体在体内会被快速清除。在这项新的研究中，研究人员采用了一种新型可注射的自组装PA，用于递送干细胞。研究人员加入了心脏保护肽（GHRPS，His-DTrp-Ala-Trp-DPhe-Lys-NH2）和基质金属蛋白酶-2（MMP-2）可降解序列Gly-Thr-Ala-Gly-Leu-Ile-Gly-Gln（GTAGLIGQ）到PA中从而制备出PA-GHRPS。结果表明，PA-GHRPS肽能够保护H9C2细胞免受H2O2诱导的氧化应激。研究人员将这两种肽混合制备出PGN水凝胶，用于包封外泌体。数据显示，PGN水凝胶能够有效地包封外泌体并确保外泌体的稳定性和持续释放。将外泌体-PGN水凝胶混合物注入大鼠心脏的梗塞边界区，与单独的外泌体处理相比，该混合物通过减少炎症、纤维化和细胞凋亡并促进血管生成来改善心肌功能。

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Human umbilical cord mesenchymal stem cell derived exosomes encapsulated in functional peptide hydrogels promote cardiac repair.

Stem cell-derived exosomes have been recognized as a potential therapy for cardiovascular disease. However, the low retention rate of exosomes after transplantation in vivo remains a major challenge in clinical applications. The aim of this study is to investigate whether human umbilical cord mesenchymal stem cell derived exosomes (UMSC-Exo) encapsulated in functional peptide hydrogels could increase the retention and stability of exosomes and improve heart function in a rat myocardial infarction model. Our results demonstrated that the PA-GHRPS peptide protected H9C2 cells from H2O2-induced oxidative stress. The gelatinization ability of PA-GHRPS can be enhanced by peptide NapFF. Therefore, these two peptides were mixed to form the PGN hydrogel, which was used to encapsulate exosomes. Our data showed that the PGN hydrogel was able to encapsulate exosomes effectively and ensured a stable and sustained release of exosomes. The exosome/PGN hydrogel mixture was injected into the infarcted border zone of rat hearts. Compared to the exosome treatment alone, the mixture improved the myocardial function by reducing inflammation, fibrosis and apoptosis, and by promoting angiogenesis. The strategy used in this study provided a practical and effective method to harness exosomes for myocardial regeneration.