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An immunometabolic patch facilitates mesenchymal stromal/stem cell therapy for myocardial infarction through a macrophage‐dependent mechanism

Mesenchymal stromal/stem cells (MSCs) have emerged as a promising approach against myocardial infarction. Due to hostile hyperinflammation, however, poor retention of transplanted cells seriously impedes their clinical applications. Proinflammatory M1 macrophages, which rely on glycolysis as their m...

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Autores principales: Xiao, Weizhang, Chen, Ming, Zhou, Wenjing, Ding, Liang, Yang, Ziying, Shao, Lianbo, Li, Jingjing, Chen, Weiqian, Shen, Zhenya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189442/
https://www.ncbi.nlm.nih.gov/pubmed/37206202
http://dx.doi.org/10.1002/btm2.10471
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author Xiao, Weizhang
Chen, Ming
Zhou, Wenjing
Ding, Liang
Yang, Ziying
Shao, Lianbo
Li, Jingjing
Chen, Weiqian
Shen, Zhenya
author_facet Xiao, Weizhang
Chen, Ming
Zhou, Wenjing
Ding, Liang
Yang, Ziying
Shao, Lianbo
Li, Jingjing
Chen, Weiqian
Shen, Zhenya
author_sort Xiao, Weizhang
collection PubMed
description Mesenchymal stromal/stem cells (MSCs) have emerged as a promising approach against myocardial infarction. Due to hostile hyperinflammation, however, poor retention of transplanted cells seriously impedes their clinical applications. Proinflammatory M1 macrophages, which rely on glycolysis as their main energy source, aggravate hyperinflammatory response and cardiac injury in ischemic region. Here, we showed that the administration of an inhibitor of glycolysis, 2‐deoxy‐d‐glucose (2‐DG), blocked the hyperinflammatory response within the ischemic myocardium and subsequently extended effective retention of transplanted MSCs. Mechanistically, 2‐DG blocked the proinflammatory polarization of macrophages and suppressed the production of inflammatory cytokines. Selective macrophage depletion abrogated this curative effect. Finally, to avoid potential organ toxicity caused by systemic inhibition of glycolysis, we developed a novel chitosan/gelatin‐based 2‐DG patch that directly adhered to the infarcted region and facilitated MSC‐mediated cardiac healing with undetectable side effects. This study pioneered the application of an immunometabolic patch in MSC‐based therapy and provided insights into the therapeutic mechanism and advantages of this innovative biomaterial.
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spelling pubmed-101894422023-05-18 An immunometabolic patch facilitates mesenchymal stromal/stem cell therapy for myocardial infarction through a macrophage‐dependent mechanism Xiao, Weizhang Chen, Ming Zhou, Wenjing Ding, Liang Yang, Ziying Shao, Lianbo Li, Jingjing Chen, Weiqian Shen, Zhenya Bioeng Transl Med Research Articles Mesenchymal stromal/stem cells (MSCs) have emerged as a promising approach against myocardial infarction. Due to hostile hyperinflammation, however, poor retention of transplanted cells seriously impedes their clinical applications. Proinflammatory M1 macrophages, which rely on glycolysis as their main energy source, aggravate hyperinflammatory response and cardiac injury in ischemic region. Here, we showed that the administration of an inhibitor of glycolysis, 2‐deoxy‐d‐glucose (2‐DG), blocked the hyperinflammatory response within the ischemic myocardium and subsequently extended effective retention of transplanted MSCs. Mechanistically, 2‐DG blocked the proinflammatory polarization of macrophages and suppressed the production of inflammatory cytokines. Selective macrophage depletion abrogated this curative effect. Finally, to avoid potential organ toxicity caused by systemic inhibition of glycolysis, we developed a novel chitosan/gelatin‐based 2‐DG patch that directly adhered to the infarcted region and facilitated MSC‐mediated cardiac healing with undetectable side effects. This study pioneered the application of an immunometabolic patch in MSC‐based therapy and provided insights into the therapeutic mechanism and advantages of this innovative biomaterial. John Wiley & Sons, Inc. 2022-12-13 /pmc/articles/PMC10189442/ /pubmed/37206202 http://dx.doi.org/10.1002/btm2.10471 Text en © 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Xiao, Weizhang
Chen, Ming
Zhou, Wenjing
Ding, Liang
Yang, Ziying
Shao, Lianbo
Li, Jingjing
Chen, Weiqian
Shen, Zhenya
An immunometabolic patch facilitates mesenchymal stromal/stem cell therapy for myocardial infarction through a macrophage‐dependent mechanism
title An immunometabolic patch facilitates mesenchymal stromal/stem cell therapy for myocardial infarction through a macrophage‐dependent mechanism
title_full An immunometabolic patch facilitates mesenchymal stromal/stem cell therapy for myocardial infarction through a macrophage‐dependent mechanism
title_fullStr An immunometabolic patch facilitates mesenchymal stromal/stem cell therapy for myocardial infarction through a macrophage‐dependent mechanism
title_full_unstemmed An immunometabolic patch facilitates mesenchymal stromal/stem cell therapy for myocardial infarction through a macrophage‐dependent mechanism
title_short An immunometabolic patch facilitates mesenchymal stromal/stem cell therapy for myocardial infarction through a macrophage‐dependent mechanism
title_sort immunometabolic patch facilitates mesenchymal stromal/stem cell therapy for myocardial infarction through a macrophage‐dependent mechanism
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189442/
https://www.ncbi.nlm.nih.gov/pubmed/37206202
http://dx.doi.org/10.1002/btm2.10471
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