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J Cardiovasc Transl Res. 2018 Oct;11(5):412-419. doi: 10.1007/s12265-018-9826-9. Epub 2018 Aug 28.

Exosome-Derived Dystrophin from Allograft Myogenic Progenitors Improves Cardiac Function in Duchenne Muscular Dystrophic Mice.

Author information

1
Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160, Pujian Road, Shanghai, 200127, China.
2
Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.
3
Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China.
4
Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, China.
5
Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160, Pujian Road, Shanghai, 200127, China. jiangmeng0919@163.com.
6
Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA. yaotang@augusta.edu.

Abstract

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.

KEYWORDS:

Cardiomyopathy; Dystrophin; Exosome; Myogenic progenitor cells

PMID:
30155598
PMCID:
PMC6212302
[Available on 2019-10-01]
DOI:
10.1007/s12265-018-9826-9
[Indexed for MEDLINE]

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