Placenta-derived mesenchymal stromal cells and their exosomes exert therapeutic effects in Duchenne muscular dystrophy

Ariel Bier, Peter Berenstein, Noam Kronfeld, Daria Morgoulis, Amotz Ziv-Av, Hodaya Goldstein, Gila Kazimirsky, Simona Cazacu, Rinat Meir, Rachela Popovtzer, Amir Dori, Chaya Brodie

Research output: Contribution to journalArticlepeer-review

109 Scopus citations


Duchenne muscular dystrophy (DMD) is a degenerative lethal, X-linked disease of skeletal and cardiac muscles caused by mutations in the dystrophin gene. Cell therapy using different cell types, including mesenchymal stromal cells (MSCs), has been considered as a potential approach for the treatment of DMD. MSCs can be obtained from autologous sources such as bone marrow and adipose tissues or from allogeneic placenta and umbilical cord. The safety and therapeutic impact of these cells has been demonstrated in pre-clinical and clinical studies and their functions are attributed to paracrine effects that are mediated by secreted cytokines and extracellular vesicles. Here, we studied the therapeutic effects of placenta-derived MSCs (PL-MSCs) and their secreted exosomes using mouse and human myoblasts from healthy controls, Duchenne patients and mdx mice. Treatment of myoblasts with conditioned medium or exosomes secreted by PL-MSCs increased the differentiation of these cells and decreased the expression of fibrogenic genes in DMD patient myoblasts. In addition, these treatments also increased the expression of utrophin in these cells. Using a quantitative miR-29c reporter, we demonstrated that the PL-MSC effects were partly mediated by the transfer of exosomal miR-29c. Intramuscular transplantation of PL-MSCs in mdx mice resulted in decreased creatine kinase levels. PL-MSCs significantly decreased the expression of TGF-β and the level of fibrosis in the diaphragm and cardiac muscles, inhibited inflammation and increased utrophin expression. In vivo imaging analyses using MSCs labeled with gold nanoparticles or fluorescent dyes demonstrated localization of the cells in the muscle tissues up to 3 weeks post treatment. Altogether, these results demonstrate that PL-MSCs and their secreted exosomes have important clinical applications in cell therapy of DMD partly via the targeted delivery of exosomal miR-29c.

Original languageEnglish
Pages (from-to)67-78
Number of pages12
StatePublished - Aug 2018

Bibliographical note

Publisher Copyright:
© 2018


This study was supported in part by the William and Karen Davidson Fund and the Hermelin Brain Tumor Center , Henry Ford Hospital, Detroit , MI, USA. The Ministry of Science and Space , Israel, A.D.I. – Association Duchenne Israel , the Israeli Parents' Duchenne/Becker Association , Life for Alon Foundation , Science in Action Ltd . and ExoStem Biotec, Israel . We thank Itay Lazar, Irit Shoval and Avi Jacob from the Imaging Core Facility, Bar-Ilan University, for their help with the ImageStream system and the confocal microscopy analyses, respectively.

FundersFunder number
Hermelin Brain Tumor Center
William and Karen Davidson Fund
Henry Ford Health System


    • Duchenne muscular dystrophy
    • Exosomes
    • Mesenchymal stem cells
    • Muscle
    • Placenta
    • miR-29


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