Exosome-Derived Dystrophin from Allograft Myogenic Progenitors Improves Cardiac Function in Duchenne Muscular Dystrophic Mice
- 411 Downloads
Progressive cardiomyocyte loss in Duchenne muscular dystrophy (DMD) leads to cardiac fibrosis, cardiomyopathy, and eventually heart failure. In the present study, we observed that myogenic progenitor cells (MPC) carry mRNA for the dystrophin gene. We tested whether cardiac function can be improved in DMD by allograft transplantation of MPC-derived exosomes (MPC-Exo) into the heart to restore dystrophin protein expression. Exo from C2C12 cells (an MPC cell line) or vehicle were delivered locally into the hearts of MDX mice. After 2 days of treatment, we observed that MPC-Exo restored dystrophin expression in the hearts of MDX mice, which correlated with improved myocardial function in dystrophin-deficient MDX mouse hearts. In conclusion, this study demonstrated that allogeneic WT-MPC-Exo transplantation transiently restored dystrophin gene expression and improved cardiac function in MDX mice, suggesting that allogenic exosomal delivery may serve as an alternative treatment for cardiomyopathy of DMD.
KeywordsDystrophin Exosome Myogenic progenitor cells Cardiomyopathy
I. Kim, N.L. Weintraub, and Y. Tang were partially supported by the American Heart Association: GRNT31430008, NIH-AR070029, NIH-HL086555, NIH-HL134354, and NIH -HL12425.
Compliance with Ethical Standards
This article does not contain any studies with human participants performed by any of the authors.
Animals were handled according to approved protocols and animal welfare regulations of the Institutional Animal Care and Use Committee of the Medical College of Georgia/Augusta University.
Conflict of Interest
The authors declare that they have no conflict of interest.
- 3.D’Amario, D., Amodeo, A., Adorisio, R., Tiziano, F. D., Leone, A. M., Perri, G., et al. (2017). A current approach to heart failure in Duchenne muscular dystrophy. Heart (British Cardiac Society)., 103(22), 1770–1779.Google Scholar
- 15.Bayoumi AS, Park KM, Wang Y, Teoh JP, Aonuma T, Tang Y, et al. A carvedilol-responsive microRNA, miR-125b-5p protects the heart from acute myocardial infarction by repressing pro-apoptotic bak1 and klf13 in cardiomyocytes. Journal of molecular and cellular cardiology. 2018;114:72–82.CrossRefGoogle Scholar
- 16.Liu, N., Williams, A. H., Maxeiner, J. M., Bezprozvannaya, S., Shelton, J. M., Richardson, J. A., et al. (2012). microRNA-206 promotes skeletal muscle regeneration and delays progression of Duchenne muscular dystrophy in mice. The Journal of Clinical Investigation, 122(6), 2054–2065.CrossRefGoogle Scholar
- 19.McDonald CM, Campbell C, Torricelli RE, Finkel RS, Flanigan KM, Goemans N, et al. Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet (London, England). 2017;390(10101):1489–1498.Google Scholar