Head-to-head comparison of relevant cell sources of small extracellular vesicles for cardiac repair: Superiority of embryonic stem cellsAstraZeneca India Private Limited, Neville Tower 11th Floor, Ramanujan IT SEZ, Rajv Gandhi Salai (OMR), Taramani, Tamil Nadu, Chennai, India.
Discovery Sciences, Oligo Assay Development, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden ; Anjarium Biosciences AG, Schlieren, Switzerland.
Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden.
Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden.
Discovery Sciences, Oligo Assay Development, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden ; Pharmaceutical Sciences, Advanced Drug Delivery, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden.
Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden.
Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden.
Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden.
Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden.
AstraZeneca India Private Limited, Neville Tower 11th Floor, Ramanujan IT SEZ, Rajv Gandhi Salai (OMR), Taramani, Tamil Nadu, Chennai, India.
Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden.
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden.
Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden.
Discovery Sciences, Oligo Assay Development, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden.
University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment. Chief Medical Office, Global Patient Safety, AstraZeneca, Mölndal, Sweden. (Translational Bioinformatics)
Department of Cardiovascular Surgery, Hôpital Européen Georges Pompidou, Université de Paris, PARCC, INSERM, Paris, France.
Discovery Sciences, Oligo Assay Development, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden.
Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden.
Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden.
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2024 (English)In: Journal of Extracellular Vesicles, E-ISSN 2001-3078, Vol. 13, no 5, article id e12445
Article in journal (Refereed) Published
Abstract [en]
Small extracellular vesicles (sEV) derived from various cell sources have been demonstrated to enhance cardiac function in preclinical models of myocardial infarction (MI). The aim of this study was to compare different sources of sEV for cardiac repair and determine the most effective one, which nowadays remains limited. We comprehensively assessed the efficacy of sEV obtained from human primary bone marrow mesenchymal stromal cells (BM-MSC), human immortalized MSC (hTERT-MSC), human embryonic stem cells (ESC), ESC-derived cardiac progenitor cells (CPC), human ESC-derived cardiomyocytes (CM), and human primary ventricular cardiac fibroblasts (VCF), in in vitro models of cardiac repair. ESC-derived sEV (ESC-sEV) exhibited the best pro-angiogenic and anti-fibrotic effects in vitro. Then, we evaluated the functionality of the sEV with the most promising performances in vitro, in a murine model of MI-reperfusion injury (IRI) and analysed their RNA and protein compositions. In vivo, ESC-sEV provided the most favourable outcome after MI by reducing adverse cardiac remodelling through down-regulating fibrosis and increasing angiogenesis. Furthermore, transcriptomic, and proteomic characterizations of sEV derived from hTERT-MSC, ESC, and CPC revealed factors in ESC-sEV that potentially drove the observed functions. In conclusion, ESC-sEV holds great promise as a cell-free treatment for promoting cardiac repair following MI.
Place, publisher, year, edition, pages
John Wiley & Sons, 2024. Vol. 13, no 5, article id e12445
Keywords [en]
angiogenesis, fibrosis, immunomodulation, myocardial ischaemia-reperfusion injury, regeneration, small extracellular vesicles, adverse outcome, antifibrotic activity, Article, BMSC cell line, cardiac muscle cell, cardiac stem cell, cell function, cell therapy, clinical effectiveness, controlled study, down regulation, exosome, fibroblast, heart surgery, human, human cell, human embryonic stem cell, immortalized cell line, in vitro study, in vivo study, myocardial ischemia reperfusion injury, outcome assessment, protein content, proteomics, RNA analysis, transcriptomics
National Category
Cell and Molecular Biology Cardiology and Cardiovascular Disease
Research subject
Bioinformatics
Identifiers
URN: urn:nbn:se:his:diva-23844DOI: 10.1002/jev2.12445ISI: 001214661200001PubMedID: 38711334Scopus ID: 2-s2.0-85192214646OAI: oai:DiVA.org:his-23844DiVA, id: diva2:1858216
Funder
Knowledge Foundation, 20200014
Note
CC BY 4.0 DEED
© 2024 AstraZeneca R&D and The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.
Correspondence Address: H. González-King; Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden; email: hernan.gonzalez-king@astrazeneca.com; K. Jennbacken; Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden; email: Karin.jennbacken@astrazeneca.com
Funding information: Högskolan i Skövde, Grant/Award Number: grant# 20200014
The authors of this manuscript acknowledge AstraZeneca early CVRM Cardiovascular for their resource management, to John Liddle and Stefan Geschwindner from AstraZeneca postdoc committee for their advice, to AstraZeneca Animal Sciences & Technologies staff for their in vivo support, to Märta Jansson for performing the flow cytometric characterization of cardiac progenitor cells and to Elisa Lázaro and Olga Shatnyeva from the exosome team in AstraZeneca for input and facilitating a smooth introduction to AstraZeneca’s exosome research, to the National Genomics Infrastructure in Stockholm funded by Science for Life Laboratory, the Knut and Alice Wallenberg Foundation and the Swedish Research Council, and SNIC/Uppsala Multidisciplinary Center for Advanced Computational Science for assistance with massively parallel sequencing and access to the UPPMAX computational infrastructure. We also thank M. Soriano at the core facility of electron microscopy-Centro de Investigación Príncipe Felipe. This manuscript was edited at Life Science Editors. This work was supported by the University of Skövde under grants from the Swedish Knowledge foundation [grant # 20200014].
2024-05-162024-05-162025-02-10Bibliographically approved