Interpenetrating network hydrogel-loaded embryonic stem cell-derived endocardial cells improves cardiac function after myocardial infarction

Abstract Background With an in-depth understanding of cardiac cell differentiation, cell therapy derived from stem cells has shown promising therapeutic effects in the treatment of myocardial infarction (MI). Although many types of cardiac or noncardiac cells have been found to play protective roles...

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Main Authors: Boshi Liu, Laiping Zhang, Xiao Guan, Jie Liu, Weinian Shou, Xin Chen, Xiaohui Li, Dayan Cao
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-025-06603-2
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author Boshi Liu
Laiping Zhang
Xiao Guan
Jie Liu
Weinian Shou
Xin Chen
Xiaohui Li
Dayan Cao
author_facet Boshi Liu
Laiping Zhang
Xiao Guan
Jie Liu
Weinian Shou
Xin Chen
Xiaohui Li
Dayan Cao
author_sort Boshi Liu
collection DOAJ
description Abstract Background With an in-depth understanding of cardiac cell differentiation, cell therapy derived from stem cells has shown promising therapeutic effects in the treatment of myocardial infarction (MI). Although many types of cardiac or noncardiac cells have been found to play protective roles in MI, the specific role of endocardial cells (ECCs) in MI has not been reported. Methods The current study was designed to determine whether human embryonic stem cell (hESC)-derived endocardial cells (hESC-ECCs) could be protective against MI. We first developed a cell delivery system by constructing a photosensitive interpenetrating network hydrogel consisting of gelatin methacryloyl (GelMA) and silk fibroin methacryloyl (SilMA). The sorted hESC-ECCs were loaded into the delivery system and then injected into the pericardium cavity of the MI rats. Results These results show that the cell delivery system has good biocompatibility. Moreover, the delivered endocardial cells improved cardiac function and delayed capillary atrophy after MI. Further mechanistic analysis revealed that hESC-ECCs protect the mitochondria of cardiomyocytes from damage under oxidative stress and potentially promote the angiogenesis of cardiac endothelial cells. Conclusion Our results demonstrated that hESC-ECCs have the potential to serve as a cell therapy strategy for MI treatment by maintaining cardiomyocyte survival and facilitating angiogenesis.
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issn 1479-5876
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publishDate 2025-05-01
publisher BMC
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series Journal of Translational Medicine
spelling doaj-art-ad1c8edaf58c414c85744a9d018fe0592025-08-20T03:22:08ZengBMCJournal of Translational Medicine1479-58762025-05-0123111710.1186/s12967-025-06603-2Interpenetrating network hydrogel-loaded embryonic stem cell-derived endocardial cells improves cardiac function after myocardial infarctionBoshi Liu0Laiping Zhang1Xiao Guan2Jie Liu3Weinian Shou4Xin Chen5Xiaohui Li6Dayan Cao7Institute of Materia Medica, Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Army Medical University)Institute of Materia Medica, Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Army Medical University)Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing Medical and Pharmaceutical CollegeInstitute of Materia Medica, Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Army Medical University)Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of MedicineInstitute of Materia Medica, Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Army Medical University)Institute of Materia Medica, Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Army Medical University)Institute of Materia Medica, Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Army Medical University)Abstract Background With an in-depth understanding of cardiac cell differentiation, cell therapy derived from stem cells has shown promising therapeutic effects in the treatment of myocardial infarction (MI). Although many types of cardiac or noncardiac cells have been found to play protective roles in MI, the specific role of endocardial cells (ECCs) in MI has not been reported. Methods The current study was designed to determine whether human embryonic stem cell (hESC)-derived endocardial cells (hESC-ECCs) could be protective against MI. We first developed a cell delivery system by constructing a photosensitive interpenetrating network hydrogel consisting of gelatin methacryloyl (GelMA) and silk fibroin methacryloyl (SilMA). The sorted hESC-ECCs were loaded into the delivery system and then injected into the pericardium cavity of the MI rats. Results These results show that the cell delivery system has good biocompatibility. Moreover, the delivered endocardial cells improved cardiac function and delayed capillary atrophy after MI. Further mechanistic analysis revealed that hESC-ECCs protect the mitochondria of cardiomyocytes from damage under oxidative stress and potentially promote the angiogenesis of cardiac endothelial cells. Conclusion Our results demonstrated that hESC-ECCs have the potential to serve as a cell therapy strategy for MI treatment by maintaining cardiomyocyte survival and facilitating angiogenesis.https://doi.org/10.1186/s12967-025-06603-2Cell delivery systemEmbryonic stem cellsEndocardial cellsMyocardial infarction
spellingShingle Boshi Liu
Laiping Zhang
Xiao Guan
Jie Liu
Weinian Shou
Xin Chen
Xiaohui Li
Dayan Cao
Interpenetrating network hydrogel-loaded embryonic stem cell-derived endocardial cells improves cardiac function after myocardial infarction
Journal of Translational Medicine
Cell delivery system
Embryonic stem cells
Endocardial cells
Myocardial infarction
title Interpenetrating network hydrogel-loaded embryonic stem cell-derived endocardial cells improves cardiac function after myocardial infarction
title_full Interpenetrating network hydrogel-loaded embryonic stem cell-derived endocardial cells improves cardiac function after myocardial infarction
title_fullStr Interpenetrating network hydrogel-loaded embryonic stem cell-derived endocardial cells improves cardiac function after myocardial infarction
title_full_unstemmed Interpenetrating network hydrogel-loaded embryonic stem cell-derived endocardial cells improves cardiac function after myocardial infarction
title_short Interpenetrating network hydrogel-loaded embryonic stem cell-derived endocardial cells improves cardiac function after myocardial infarction
title_sort interpenetrating network hydrogel loaded embryonic stem cell derived endocardial cells improves cardiac function after myocardial infarction
topic Cell delivery system
Embryonic stem cells
Endocardial cells
Myocardial infarction
url https://doi.org/10.1186/s12967-025-06603-2
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