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基于人羊膜上皮干细胞片的抗氧化聚氨酯支架的心脏外膜移植治疗心肌梗死。

Epicardial transplantation of antioxidant polyurethane scaffold based human amniotic epithelial stem cell patch for myocardial infarction treatment.

机构信息

Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine of Sir Run Run Shaw Hospital, Zhejiang University-Lishui Joint Innovation Center for Life and Health, Zhejiang University, Hangzhou, 310058, China.

College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.

出版信息

Nat Commun. 2024 Oct 22;15(1):9105. doi: 10.1038/s41467-024-53531-8.

Abstract

Myocardial infarction (MI) is a leading cause of death globally. Stem cell therapy is considered a potential strategy for MI treatment. Transplantation of classic stem cells including embryonic, induced pluripotent and cardiac stem cells exhibited certain repairing effect on MI via supplementing cardiomyocytes, however, their clinical applications were blocked by problems of cell survival, differentiation, functional activity and also biosafety and ethical concerns. Here, we introduced human amniotic epithelial stem cells (hAESCs) featured with immunomodulatory activities, immune-privilege and biosafety, for constructing a stem cell cardiac patch based on porous antioxidant polyurethane (PUR), which demonstrated decent hAESCs compatibility. In rats, the administration of PUR-hAESC patch significantly reduced fibrosis and facilitated vascularization in myocardium after MI and consequently improved cardiac remodeling and function. Mechanistically, the patch provides a beneficial microenvironment for cardiac repair by facilitating a desirable immune response, paracrine modulation and limited oxidative milieu. Our findings may provide a potential therapeutic strategy for MI.

摘要

心肌梗死(MI)是全球范围内主要的死亡原因。干细胞疗法被认为是治疗 MI 的一种有潜力的策略。移植经典的干细胞,包括胚胎干细胞、诱导多能干细胞和心脏干细胞,通过补充心肌细胞,对 MI 具有一定的修复作用,但由于细胞存活、分化、功能活性以及生物安全性和伦理问题,其临床应用受到了阻碍。在这里,我们介绍了具有免疫调节活性、免疫豁免和生物安全性的人羊膜上皮干细胞(hAESCs),用于构建基于多孔抗氧化聚氨酯(PUR)的干细胞心脏贴片,该贴片表现出良好的 hAESCs 相容性。在大鼠中,PUR-hAESC 贴片的给药显著减少了 MI 后心肌中的纤维化,并促进了血管生成,从而改善了心脏重构和功能。从机制上讲,该贴片通过促进理想的免疫反应、旁分泌调节和有限的氧化环境,为心脏修复提供了有益的微环境。我们的研究结果可能为 MI 提供了一种潜在的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1387/11496666/5006a09ce486/41467_2024_53531_Fig1_HTML.jpg

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