Fabrication of Tβ4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralization

作者：Chen, Peier; Ning, Xiaodong; Li, Weirun; Pan, Yuxuan; Wang, Ling; Li, Hekai; Fan, Xianglin; Zhang, Jiexin; Luo, Tiantian; Wu, Yaobin^*; Ou, Caiwen^*; Chen, Minsheng^*

来源：Bioactive Materials, 2022, 14: 416-429.

DOI：10.1016/j.bioactmat.2022.01.029

• Artificial stem cells
• Exosomes
• Myocardial infarction
• Coronary collateralization

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 T beta 4-exosomes (T beta 4-ASCs) by encapsulating specific exosomes within microspheres using microfluidics technology. The results show that T beta 4-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 T beta 4-ASC-derived exosomes can enhance the angiogenic capacity of coronary endothelial cells (CAECs) via the miR-17-5p/PHD3/Hif-1 alpha pathway. In brief, as artificial stem cells, T beta 4-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.

• 单位
  南方医科大学