Myocardial infarction (MI) is the cardiac emergency that may leads to myocardial necrosis. Mesenchymal stem cells (MSCs) could be used to induce myocardial differentiation. However, the efficiency remains low. The aim of this study is to explore whether miR-19a/19b could enhance the therapeutic potential of mesenchymal stem cells in MI. Myocardial infarction mouse model was established using coronary artery ligation. Cardiac functional recovery was detected by Masson’s trichrome staining. Under hypoxic condition, miR-19a/19b expression levels decreased in bone marrow-derived MSCs (BM-MSCs). MiR-19a/19b suppressed the proliferation of MSCs under hypoxic condition. After cell engraftment, miR-19a/19b promoted survival of MSCs. Mechanically, miR-19a/19b inhibited inflammatory cells infiltration into myocardium cells. Moreover, MSCs-miR-19a/19b improves cardiac functional recovery in diabetic MI mice models. All the results indicated that miR-19a/19b improves the therapeutic potential of mesenchymal stem cells in a mouse model of myocardial infarction.
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van Rooij E. Cardiac repair after myocardial infarction. N Engl J Med. 2016;374:85–7.
Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012;60:1581–98.
Anderson JL, Morrow DA. Acute myocardial Infarction. N Engl J Med. 2017;376:2053–64.
Xin M, Olson EN, Bassel-Duby R. Mending broken hearts: cardiac development as a basis for adult heart regeneration and repair. Nat Rev Mol Cell Biol. 2013;14:529–41.
Gao F, Kataoka M, Liu N, Liang T, Huang ZP, Gu F, et al. Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction. Nat Commun. 2019;10:1802.
Williams AR, Hare JM. Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ Res. 2011;109:923–40.
Cai M, Shen R, Song L, Lu M, Wang J, Zhao S, et al. Bone marrow mesenchymal stem cells (BM-MSCs) improve heart function in swine myocardial infarction model through paracrine effects. Sci Rep. 2016;6:28250.
Karantalis V, Hare JM. Use of mesenchymal stem cells for therapy of cardiac disease. Circ Res. 2015;116:1413–30.
Wen Z, Zheng S, Zhou C, Wang J, Wang T. Repair mechanisms of bone marrow mesenchymal stem cells in myocardial infarction. J Cell Mol Med. 2011;15:1032–43.
Majka M, Sulkowski M, Badyra B, Musialek P. Concise review: mesenchymal stem cells in cardiovascular regeneration: emerging research directions and clinical applications. Stem Cells Transl Med. 2017;6:1859–67.
Yan W, Guo Y, Tao L, Lau WB, Gan L, Yan Z. et al. C1q/tumor necrosis factor-related protein-9 regulates the fate of implanted mesenchymal stem cells and mobilizes their protective effects against ischemic heart injury via multiple novel signaling pathways. Circulation. 2017;136:2162–77.
Khan M, Ali F, Mohsin S, Akhtar S, Mehmood A, Choudhery MS, et al. Preconditioning diabetic mesenchymal stem cells with myogenic medium increases their ability to repair diabetic heart. Stem Cell Res Ther. 2013;4:58.
Hu X, Xu Y, Zhong Z, Wu Y, Zhao J, Wang Y, et al. A large-scale investigation of hypoxia-preconditioned allogeneic mesenchymal stem cells for myocardial repair in nonhuman primates: paracrine activity without remuscularization. Circ Res. 2016;118:970–83.
Ouchida M, Kanzaki H, Ito S, Hanafusa H, Jitsumori Y, Tamaru S, et al. Novel direct targets of miR-19a identified in breast cancer cells by a quantitative proteomic approach. PLoS ONE. 2012;7:e44095.
Chen J, Huang ZP, Seok HY, Ding J, Kataoka M, Zhang Z, et al. mir-17-92 cluster is required for and sufficient to induce cardiomyocyte proliferation in postnatal and adult hearts. Circ Res. 2013;112:1557–66.
Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell. 2003;115:787–98.
Soleimani M, Nadri S. A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow. Nat Protoc. 2009;4:102–6.
Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39:119–77.
Ryan TJ, Anderson JL, Antman EM, Braniff BA, Brooks NH, Califf RM, et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). Circulation. 1996;94:2341–50.
Spath NB, Mills NL, Cruden NL. Novel cardioprotective and regenerative therapies in acute myocardial infarction: a review of recent and ongoing clinical trials. Future Cardiol. 2016;12:655–72.
Eulalio A, Mano M, Dal Ferro M, Zentilin L, Sinagra G, Zacchigna S, et al. Functional screening identifies miRNAs inducing cardiac regeneration. Nature. 2012;492:376–81.
Tian Y, Liu Y, Wang T, Zhou N, Kong J, Chen L, et al. A microRNA-Hippo pathway that promotes cardiomyocyte proliferation and cardiac regeneration in mice. Sci Transl Med. 2015;7:279ra38.
Yang Y, Cheng HW, Qiu Y, Dupee D, Noonan M, Lin YD, et al. MicroRNA-34a plays a key role in cardiac repair and regeneration following myocardial infarction. Circ Res. 2015;117:450–9.
Gurha P. MicroRNAs in cardiovascular disease. Curr Opin Cardiol. 2016;31:249–54.
Aguirre A, Montserrat N, Zacchigna S, Nivet E, Hishida T, Krause MN, et al. In vivo activation of a conserved microRNA program induces mammalian heart regeneration. Cell Stem Cell. 2014;15:589–604.
Sager HB, Dutta P, Dahlman JE, Hulsmans M, Courties G, Sun Y, et al. RNAi targeting multiple cell adhesion molecules reduces immune cell recruitment and vascular inflammation after myocardial infarction. Sci Transl Med. 2016;8:342ra80.
Richart A, Reddy M, Natoli A, Heywood S, Khalaji M, Lancaster G. et al. Abstract 329: ApoA-I nanoparticles (CSL-111) directly modulates inflammatory cells after myocardial infarction in mice. Arterioscler Thromb Vasc Biol. 2019;39 Suppl_1:A329-A329.
King KR, Aguirre AD, Ye YX, Sun Y, Roh JD, Ng RP Jr., et al. IRF3 and type I interferons fuel a fatal response to myocardial infarction. Nat Med. 2017;23:1481–7.
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Chen, C., Chen, T., Li, Y. et al. miR-19a/19b improves the therapeutic potential of mesenchymal stem cells in a mouse model of myocardial infarction. Gene Ther (2020). https://doi.org/10.1038/s41434-020-0122-3