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GATA-4-expressing mouse bone marrow mesenchymal stem cells improve cardiac function after myocardial infarction via secreted exosomes
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GATA-4-expressing mouse bone marrow mesenchymal stem cells improve cardiac function after myocardial infarction via secreted exosomes
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Journal Article
GATA-4-expressing mouse bone marrow mesenchymal stem cells improve cardiac function after myocardial infarction via secreted exosomes
2018
Overview
This study aimed to investigate whether exosomes secreted by mouse GATA-4-expressing bone marrow mesenchymal stem cells (BMSCs) could induce BMSC differentiation into myocyte precursors, decrease cardiomyocyte apoptosis, and improve cardiac function following myocardial infarction (MI). BMSCs were transduced with a lentivirus carrying a doxycycline (DOX)-inducible
GATA-4
or control lentivirus, and secreted exosomes from these BMSCs were collected and co-cultured with BMSCs or cardiomyocytes under hypoxic and serum free conditions. Furthermore, exosomes were injected into mice 48 h after MI. Cardiac function was evaluated by echocardiography at 48, 72, and 96 h after exosome treatment. Quantitative PCR showed that co-culture of BMSCs with GATA-4-BMSC exosomes increased cardiomyocyte-related marker expression. Co-culture of GATA-4-BMSC exosomes with cardiomyocytes in anoxic conditions decreased apoptosis as detected by flow cytometry. Injection of GATA-4-BMSC exosomes in mice 48 h after MI increased cardiac function over the next 96 h; increased cardiac blood vessel density and number of c-kit-positive cells and decreased apoptotic cardiomyocyte cells were also observed. Differential expression of candidate differentiation- and apoptosis-related miRNAs and proteins that may mediate these effects was also identified. Exosomes isolated from GATA-4-expressing BMSCs induce differentiation of BMSCs into cardiomyocyte-like cells, decrease anoxia-induced cardiomyocyte apoptosis, and improve myocardial function after infarction.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 14/5
/ 38/61
/ 631/443
/ Animals
/ Anoxia
/ Cell Differentiation - genetics
/ Exosomes
/ GATA4 Transcription Factor - genetics
/ GATA4 Transcription Factor - metabolism
/ Heart
/ Humanities and Social Sciences
/ Hypoxia
/ Male
/ Mesenchymal Stem Cell Transplantation - methods
/ Mesenchymal Stem Cells - cytology
/ Mesenchymal Stem Cells - metabolism
/ Myocardial Infarction - genetics
/ Myocardial Infarction - metabolism
/ Myocardial Infarction - therapy
/ Myocytes
/ Myocytes, Cardiac - cytology
/ Myocytes, Cardiac - metabolism
/ Science
