The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Exosomes secreted from GATA-4 overexpressing mesenchymal stem cells serve as a reservoir of anti-apoptotic microRNAs for cardioprotection
Open accessAbstract
Background Exosomes play an important role in intercellular signaling and exert regulatory function by carrying bioactive molecules. This study investigated the cardioprotective capabilities of exosomes derived from mesenchymal stem cells (MSC) overexpressing GATA-4 (MSCGATA-4) and its underlying mechanisms through delivering miroRNAs (miRs) to regulate the target proteins in recipient cells. Methods and Results Exosomes were isolated and purified from MSCGATA-4 (ExoGATA-4) and control MSCs (ExoNull). Cell injury was investigated in primary cultured rat neonatal cardiomyocytes (CM) and in the rat heart. Exosomes contributed to increased CM survival, reduced CM apoptosis, and preserved mitochondrial membrane potential in CM cultured under a hypoxic environment. Direct intramyocardial transplantation of exosomes at the border of an ischemic region following ligation of the left anterior descending coronary artery significantly restored cardiac contractile function and reduced infarct size. Real-time PCR revealed that several anti-apoptotic miRs were highly expressed in ExoGATA-4. Rapid internalization of ExoGATA-4 by CM was documented using time-lapse imaging. Subsequent expression of these miRs, particularly miR-19a was higher in CM and in the myocardium treated with ExoGATA-4 compared to those treated with ExoNull. The enhanced protective effects observed in CM were diminished by inhibition of miR-19a. The expression level of PTEN, a predicted target of miR-19a, was reduced in CM treated with ExoGATA-4, which resulted in the activation of the Akt and ERK signaling pathways. Conclusions ExoGATA-4 transferred miRs into damaged CM, triggering activation of the cell survival signaling pathway.
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Concise review: MSC-derived exosomes for cell-free therapy
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Exosome Theranostics: Biology and Translational Medicine
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Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases
Shi, Y., Wang, Y., Li, Q., Liu, K., Hou, J., Shao, C., & Wang, Y. (2018) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0023-5 · Cited by 1,223
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Mesenchymal stem cell-derived extracellular vesicles: novel frontiers in regenerative medicine
Keshtkar, S., Azarpira, N., & Ghahremani, M. H. (2018) · Stem Cell Research & Therapy · doi:10.1186/s13287-018-0791-7 · Cited by 907
Metadata
- Authors
- Yu, B., Kim, H. W., Gong, M., Wang, J., Millard, R. W., Wang, Y., Ashraf, M., & Xu, M.
- Venue
- International Journal of Cardiology
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 182
- Pages
- 349-360
- ISSN
- 0167-5273 (ISSN-L)
- OpenAlex
- W2090335937
- Cited by
- 473
- References
- 37
- FWCI
- 9.25
- Type
- journal article
- Language
- en
- Open access
- green
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- Yu, B., Kim, H. W., Gong, M., Wang, J., Millard, R. W., Wang, Y., Ashraf, M., & Xu, M. (2015). Exosomes secreted from GATA-4 overexpressing mesenchymal stem cells serve as a reservoir of anti-apoptotic microRNAs for cardioprotection. International Journal of Cardiology. https://doi.org/10.1016/j.ijcard.2014.12.043
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