Fabrication of Tβ4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralization.
Fabrication of Tβ4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralization.
复制标题
通过改善冠状动脉抵押治疗心肌梗死治疗 Tβ4-外泌体释放人工干细胞的制造
DOI：
10.1016/j.bioactmat.2022.01.029
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发表时间：
2022-08
影响因子：
18.9
通讯作者：
Chen M
中科院分区：
文献类型：
--
作者：
Chen P;Ning X;Li W;Pan Y;Wang L;Li H;Fan X;Zhang J;Luo T;Wu Y;Ou C;Chen M
目前，干细胞移植在心脏修复中的应用受到免疫排斥和细胞活性差等缺点的限制。虽然直接注射外切体可以达到与干细胞移植相似的疗效，但高清晰度阻碍了其在临床上的应用。以往的报道表明，对于错过了减轻心肌缺血的最佳手术时机的人来说，冠状动脉侧支循环的诱导可能是一种理想的辅助治疗方法。在本研究中，为了模拟干细胞的旁分泌和生物学活性，我们利用微流控技术将特定的外切体包裹在微球中，开发了能够持续释放Tβ4-外切体(Tβ4-ASCs)的人工干细胞。结果表明，T-β-4-ASCs能显著促进心肌梗死周边冠脉的侧支循环，其治疗效果优于直接注射外切体。此外，为了更好地了解它的作用机制，我们还证明了T-β4-Asc来源的外体可以通过miR-17-5p/PHD3/Hif-1α途径增强冠状动脉内皮细胞的血管生成能力。总之，T-β-4-Asc作为人工干细胞，可以持续释放功能性外体，刺激心肌梗死后侧支循环的形成，为临床血管重建提供了一种可行的替代方法。T-β4-ASCs是一种将微球与工程化外切体相结合形成的人工干细胞，可在心肌梗死区域缓慢、持续地释放T-β4-外切体。Tβ4-ASCs持续释放的特异性Tβ4-exOS可通过促进冠状动脉内皮细胞的血管生成来促进冠脉侧支循环的形成，满足精密医学的要求。受干细胞旁分泌的启发，我们利用微流控技术将工程Tβ4-exosome负载到Tβ4-exosome上，构建了人工干细胞(T-asc)。Tβ4-Asc通过缓慢持续释放工程化Tβ4-外切体，刺激心肌梗死区冠状动脉侧支循环的形成。Tβ4-Asc通过miR-17-5p/PHD3/Hif-1α信号通路改善冠脉侧支循环。
Currently, stem cell transplantations in cardiac repair are limited owing to disadvantages, such as immunological rejection and poor cell viability. Although direct injection of exosomes can have a curative effect similar to that of stem cell transplantation, high clearance hinders its application in clinical practice. Previous reports suggested that induction of coronary collateralization can be a desired method of adjunctive therapy for someone who had missed the optimal operation time to attenuate myocardial ischemia. In this study, to mimic the paracrine and biological activity of stem cells, we developed artificial stem cells that can continuously release Tβ4-exosomes (Tβ4-ASCs) by encapsulating specific exosomes within microspheres using microfluidics technology. The results show that Tβ4-ASCs can greatly promote coronary collateralization in the periphery of the myocardial infarcted area, and its therapeutic effect is superior to that of directly injecting the exosomes. In addition, to better understand how it works, we demonstrated that the Tβ4-ASC-derived exosomes can enhance the angiogenic capacity of coronary endothelial cells (CAECs) via the miR-17-5p/PHD3/Hif-1α pathway. In brief, as artificial stem cells, Tβ4-ASCs can constantly release functional exosomes and stimulate the formation of collateral circulation after myocardial infarction, providing a feasible and alternative method for clinical revascularization. Tβ4-ASCs, an artificial stem cells developed by combining microspheres and engineered exosomes, can release Tβ4-exosomes slowly and continuously in myocardial infarcted area. Specific Tβ4-EXOs released constantly from Tβ4-ASCs can enhance the formation of coronary collateralization by promoting the angiogenesis of coronary artery endothelial cells (CAECs), meeting the requirements of precision medicine. Inspired by the paracrine of stem cells, we fabricated artificial stem cells (Tβ4-ASCs) by loading engineered Tβ4-exosomes with microspheres using microfluidics technology. Tβ4-ASCs stimulate the formation of coronary collateralization in myocardial infarcted area through a slowly sustained release of engineered Tβ4-exosomes. Tβ4-ASCs improve coronary collateralization via the miR-17-5p/PHD3/Hif-1α signaling pathway.
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心脏损伤中细胞外囊泡的靶向递送
影响因子：
12.4
作者：
Chen P;Wang L;Fan X;Ning X;Yu B;Ou C;Chen M
通讯作者：
Chen M
DOI：
10.1007/978-1-4939-3584-0_17
发表时间：
2016-01-01
期刊：
MESENCHYMAL STEM CELLS, 2 EDITION
影响因子：
--
作者：
Lian, Qizhou;Zhang, Yuelin;Tse, Hung-Fat
通讯作者：
Tse, Hung-Fat
影响因子：
28.1
作者：
Liu, Shiyu;Chen, Xin;Jin, Yan
通讯作者：
Jin, Yan
影响因子：
4
作者：
Liang, Xiaolei;Zhang, Lina;Zhao, Robert Chunhua
通讯作者：
Zhao, Robert Chunhua
影响因子：
6.1
作者：
Krutkramelis K;Xia B;Oakey J
通讯作者：
Oakey J