Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

miR-19a/19b improves the therapeutic potential of mesenchymal stem cells in a mouse model of myocardial infarction

Gene Therapy volume 28, pages 29–37 (2021)Cite this article

Subjects

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Characterization of BM-MSCs and miR-19a/19b expression under hypoxic condition.
Fig. 2: miR-19a/19b facilitates survival of BM-MSCs under hypoxic condition.
Fig. 3: miR-19a/19b facilitates survival of BM-MSCs after cell engraftment.
Fig. 4: Transplantation of MSCs-miR-19a/19b suppresses infiltration of inflammatory cells and expression of pro-inflammatory cytokines in the myocardium.
Fig. 5: Transplantation of MSCs-miR-19a/19b improves cardiac functional recovery in mice model of diabetic MI.

Similar content being viewed by others

References

  1. van Rooij E. Cardiac repair after myocardial infarction. N Engl J Med. 2016;374:85–7.

    Article  Google Scholar 

  2. 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.

    Article  Google Scholar 

  3. Anderson JL, Morrow DA. Acute myocardial Infarction. N Engl J Med. 2017;376:2053–64.

    Article  CAS  Google Scholar 

  4. 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.

    Article  CAS  Google Scholar 

  5. 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.

    Article  Google Scholar 

  6. Williams AR, Hare JM. Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ Res. 2011;109:923–40.

    Article  CAS  Google Scholar 

  7. 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.

    Article  CAS  Google Scholar 

  8. Karantalis V, Hare JM. Use of mesenchymal stem cells for therapy of cardiac disease. Circ Res. 2015;116:1413–30.

    Article  CAS  Google Scholar 

  9. 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.

    Article  CAS  Google Scholar 

  10. 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.

    Article  Google Scholar 

  11. 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.

    Article  CAS  Google Scholar 

  12. 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.

    Article  CAS  Google Scholar 

  13. 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.

    Article  CAS  Google Scholar 

  14. 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.

    Article  CAS  Google Scholar 

  15. 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.

    Article  CAS  Google Scholar 

  16. Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell. 2003;115:787–98.

    Article  CAS  Google Scholar 

  17. Soleimani M, Nadri S. A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow. Nat Protoc. 2009;4:102–6.

    Article  CAS  Google Scholar 

  18. 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.

    Article  Google Scholar 

  19. 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.

    Article  CAS  Google Scholar 

  20. 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.

    Article  CAS  Google Scholar 

  21. 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.

    Article  CAS  Google Scholar 

  22. 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.

    Article  Google Scholar 

  23. 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.

    Article  CAS  Google Scholar 

  24. Gurha P. MicroRNAs in cardiovascular disease. Curr Opin Cardiol. 2016;31:249–54.

    Article  Google Scholar 

  25. 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.

    Article  CAS  Google Scholar 

  26. 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.

    Article  Google Scholar 

  27. 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.

    Google Scholar 

  28. 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.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiology, Quanzhou First Affiliated Hospital of Fujian Medical University, No. 250, East Street, Licheng district, Quanzhou, 362000, Fujian, China

    Chengbo Chen, Tianbao Chen, Yangyi Li & Youbang Xu

Authors
  1. Chengbo Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tianbao Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yangyi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Youbang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chengbo Chen.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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 28, 29–37 (2021). https://doi.org/10.1038/s41434-020-0122-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41434-020-0122-3

This article is cited by

Search

Advanced search

Quick links