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GATA-4-expressing mouse bone marrow mesenchymal stem cells improve cardiac function after myocardial infarction via secreted exosomes
- Source :
- Scientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
- Publication Year :
- 2018
- Publisher :
- Nature Publishing Group, 2018.
-
Abstract
- 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.
- Subjects :
- Male
0301 basic medicine
Cardiac function curve
Time Factors
Myocardial Infarction
Gene Expression
lcsh:Medicine
Apoptosis
Biology
Exosomes
Mesenchymal Stem Cell Transplantation
Exosome
Flow cytometry
03 medical and health sciences
stomatognathic system
microRNA
medicine
Animals
Myocyte
Myocytes, Cardiac
lcsh:Science
Cells, Cultured
Multidisciplinary
medicine.diagnostic_test
lcsh:R
Cell Differentiation
Heart
Mesenchymal Stem Cells
Cell Hypoxia
Coculture Techniques
Microvesicles
GATA4 Transcription Factor
Cell biology
Mice, Inbred C57BL
030104 developmental biology
Real-time polymerase chain reaction
lcsh:Q
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....e03a3b1fa12cc6b7c2d80f7eb2c23491