Placenta-derived mesenchymal stromal cells and their exosomes exert therapeutic effects in Duchenne muscular dystrophy
| Autor: | Gila Kazimirsky, Amir Dori, Ariel Bier, Noam Kronfeld, Daria Morgoulis, Simona Cazacu, Rinat Meir, Peter Berenstein, Amotz Ziv-Av, Chaya Brodie, Hodaya Goldstein, Rachela Popovtzer |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Utrophin Placenta Duchenne muscular dystrophy Biophysics Metal Nanoparticles Bioengineering Exosomes Mesenchymal Stem Cell Transplantation Transfection Umbilical Cord Dystrophin Myoblasts Biomaterials Cell therapy Extracellular Vesicles 03 medical and health sciences Paracrine signalling Pregnancy Transforming Growth Factor beta medicine Animals Humans Myocyte Fluorescent Dyes business.industry Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells medicine.disease Muscular Dystrophy Duchenne Transplantation MicroRNAs 030104 developmental biology medicine.anatomical_structure Adipose Tissue Gene Expression Regulation Mechanics of Materials Culture Media Conditioned Mice Inbred mdx Ceramics and Composites Cancer research Female Gold Bone marrow business |
| Zdroj: | Biomaterials. 174:67-78 |
| ISSN: | 0142-9612 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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