Fabrication of Tβ4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving 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 i...

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Main Authors: Peier Chen, Xiaodong Ning, Weirun Li, Yuxuan Pan, Ling Wang, Hekai Li, Xianglin Fan, Jiexin Zhang, Tiantian Luo, Yaobin Wu, Caiwen Ou, Minsheng Chen
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2022-08-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X22000408
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author Peier Chen
Xiaodong Ning
Weirun Li
Yuxuan Pan
Ling Wang
Hekai Li
Xianglin Fan
Jiexin Zhang
Tiantian Luo
Yaobin Wu
Caiwen Ou
Minsheng Chen
author_facet Peier Chen
Xiaodong Ning
Weirun Li
Yuxuan Pan
Ling Wang
Hekai Li
Xianglin Fan
Jiexin Zhang
Tiantian Luo
Yaobin Wu
Caiwen Ou
Minsheng Chen
author_sort Peier Chen
collection DOAJ
description 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.
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spelling doaj.art-6eb698488c504bb0ba5b44fc626e88c12024-04-16T17:16:32ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2022-08-0114416429Fabrication of Tβ4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralizationPeier Chen0Xiaodong Ning1Weirun Li2Yuxuan Pan3Ling Wang4Hekai Li5Xianglin Fan6Jiexin Zhang7Tiantian Luo8Yaobin Wu9Caiwen Ou10Minsheng Chen11Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Department of Cardiology and Laboratory of Heart Center, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, ChinaGuangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Department of Cardiology and Laboratory of Heart Center, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, ChinaGuangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Department of Cardiology and Laboratory of Heart Center, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, ChinaGuangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Department of Cardiology and Laboratory of Heart Center, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, ChinaBiomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou, 510515, ChinaGuangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Department of Cardiology and Laboratory of Heart Center, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, ChinaGuangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Department of Cardiology and Laboratory of Heart Center, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, ChinaGuangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Department of Cardiology and Laboratory of Heart Center, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, ChinaGuangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Department of Cardiology and Laboratory of Heart Center, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, ChinaGuangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Medical Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China; Corresponding author.Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Department of Cardiology and Laboratory of Heart Center, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China; Corresponding author.Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Department of Cardiology and Laboratory of Heart Center, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2452199X22000408Artificial stem cellsExosomesMyocardial infarctionCoronary collateralization
spellingShingle Peier Chen
Xiaodong Ning
Weirun Li
Yuxuan Pan
Ling Wang
Hekai Li
Xianglin Fan
Jiexin Zhang
Tiantian Luo
Yaobin Wu
Caiwen Ou
Minsheng Chen
Fabrication of Tβ4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralization
Bioactive Materials
Artificial stem cells
Exosomes
Myocardial infarction
Coronary collateralization
title Fabrication of Tβ4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralization
title_full Fabrication of Tβ4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralization
title_fullStr Fabrication of Tβ4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralization
title_full_unstemmed Fabrication of Tβ4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralization
title_short Fabrication of Tβ4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralization
title_sort fabrication of tβ4 exosome releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralization
topic Artificial stem cells
Exosomes
Myocardial infarction
Coronary collateralization
url http://www.sciencedirect.com/science/article/pii/S2452199X22000408
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