Abstract
Improving stem cell therapy is a major goal for the treatment of muscle diseases, where physiological muscle regeneration is progressively exhausted. Vessel-associated stem cells, such as mesoangioblasts (MABs), appear to be the most promising cell type for the cell therapy for muscular dystrophies and have been shown to significantly contribute to restoration of muscle structure and function in different muscular dystrophy models. Here, we report that melanoma antigen-encoding gene (MAGE) protein necdin enhances muscle differentiation and regeneration by MABs. When necdin is constitutively overexpressed, it accelerates their differentiation and fusion in vitro and it increases their efficacy in reconstituting regenerating myofibres in the α-sarcoglycan dystrophic mouse. Moreover, necdin enhances survival when MABs are exposed to cytotoxic stimuli that mimic the inflammatory dystrophic environment. Taken together, these data demonstrate that overexpression of necdin may be a crucial tool to boost therapeutic applications of MABs in dystrophic muscle.
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Abbreviations
- Ab:
-
antibody
- αSMA:
-
alpha-smooth muscle actin
- α-SG:
-
alpha-sarcoglycan
- DMD:
-
Duchenne muscular dystrophy
- GFP:
-
green fluorescent protein
- MABs:
-
mesoangioblasts
- PDGFR:
-
platelet-derived growth factor receptor
- TA:
-
tibialis anterior
- TGFβ:
-
transforming growth factor beta
- TNFα:
-
tumor necrosis factor alpha
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Acknowledgements
This work has benefited from research funding from Telethon (GGP07013), the Italian Ministry of University and Research (PRIN 2009), the European Community's Seventh Framework Programme in the project ENDOSTEM (Grant agreement number 241440) to SB, and OPTISTEM (Grant agreement number 223098) to GC. We are also grateful to Jordi Diaz-Manera for technical help.
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Pessina, P., Conti, V., Tonlorenzi, R. et al. Necdin enhances muscle reconstitution of dystrophic muscle by vessel-associated progenitors, by promoting cell survival and myogenic differentiation. Cell Death Differ 19, 827–838 (2012). https://doi.org/10.1038/cdd.2011.160
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DOI: https://doi.org/10.1038/cdd.2011.160
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