Tags

Type your tag names separated by a space and hit enter

Placenta-derived mesenchymal stromal cells and their exosomes exert therapeutic effects in Duchenne muscular dystrophy.
Biomaterials. 2018 08; 174:67-78.B

Abstract

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.

Authors+Show Affiliations

The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.Department of Neurosurgery, Henry Ford Hospital, Detroit, MI, USA.Faculty of Engineering & Institutes of Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat-Gan, Israel.Faculty of Engineering & Institutes of Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat-Gan, Israel.Department of Neurology, Talpiot Medical Leadership Program, Chaim Sheba Medical Center, Ramat-Gan and Sackler Faculty of Medicine, Tel-Aviv University, Israel.The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel; Department of Neurosurgery, Henry Ford Hospital, Detroit, MI, USA; ExoStem Biotec, Israel. Electronic address: chaya@brodienet.om.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29783118

Citation

Bier, Ariel, et al. "Placenta-derived Mesenchymal Stromal Cells and Their Exosomes Exert Therapeutic Effects in Duchenne Muscular Dystrophy." Biomaterials, vol. 174, 2018, pp. 67-78.
Bier A, Berenstein P, Kronfeld N, et al. Placenta-derived mesenchymal stromal cells and their exosomes exert therapeutic effects in Duchenne muscular dystrophy. Biomaterials. 2018;174:67-78.
Bier, A., Berenstein, P., Kronfeld, N., Morgoulis, D., Ziv-Av, A., Goldstein, H., Kazimirsky, G., Cazacu, S., Meir, R., Popovtzer, R., Dori, A., & Brodie, C. (2018). Placenta-derived mesenchymal stromal cells and their exosomes exert therapeutic effects in Duchenne muscular dystrophy. Biomaterials, 174, 67-78. https://doi.org/10.1016/j.biomaterials.2018.04.055
Bier A, et al. Placenta-derived Mesenchymal Stromal Cells and Their Exosomes Exert Therapeutic Effects in Duchenne Muscular Dystrophy. Biomaterials. 2018;174:67-78. PubMed PMID: 29783118.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Placenta-derived mesenchymal stromal cells and their exosomes exert therapeutic effects in Duchenne muscular dystrophy. AU - Bier,Ariel, AU - Berenstein,Peter, AU - Kronfeld,Noam, AU - Morgoulis,Daria, AU - Ziv-Av,Amotz, AU - Goldstein,Hodaya, AU - Kazimirsky,Gila, AU - Cazacu,Simona, AU - Meir,Rinat, AU - Popovtzer,Rachela, AU - Dori,Amir, AU - Brodie,Chaya, Y1 - 2018/05/03/ PY - 2018/01/29/received PY - 2018/04/26/revised PY - 2018/04/29/accepted PY - 2018/5/22/pubmed PY - 2019/11/28/medline PY - 2018/5/22/entrez KW - Duchenne muscular dystrophy KW - Exosomes KW - Mesenchymal stem cells KW - Muscle KW - Placenta KW - miR-29 SP - 67 EP - 78 JF - Biomaterials JO - Biomaterials VL - 174 N2 - 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. SN - 1878-5905 UR - https://www.unboundmedicine.com/medline/citation/29783118/Placenta_derived_mesenchymal_stromal_cells_and_their_exosomes_exert_therapeutic_effects_in_Duchenne_muscular_dystrophy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0142-9612(18)30325-9 DB - PRIME DP - Unbound Medicine ER -