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Stem Cell Res. 2019 Oct 25;41:101619. doi: 10.1016/j.scr.2019.101619. [Epub ahead of print]

Characterization of mesoangioblast cell fate and improved promyogenic potential of a satellite cell-like subpopulation upon transplantation in dystrophic murine muscles.

Author information

1
Institute of Biotechnology and Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland.
2
Vital-IT, Swiss Institute of Bioinformatics, Lausanne, Switzerland.
3
Grand Valley State University, MI, USA.
4
Institute of Biotechnology and Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland; Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zürich, Switzerland.
5
Institute of Biotechnology and Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland. Electronic address: nicolas.mermod@unil.ch.

Abstract

Duchenne muscular dystrophy (DMD) is a lethal muscle-wasting disease caused by the lack of dystrophin in muscle fibers that is currently without curative treatment. Mesoangioblasts (MABs) are multipotent progenitor cells that can differentiate to a myogenic lineage and that can be used to express Dystrophin upon transplantation into muscles, in autologous gene therapy approaches. However, their fate in the muscle environment remains poorly characterized. Here, we investigated the differentiation fate of MABs following their transplantation in DMD murine muscles using a mass cytometry strategy. This allowed the identification and isolation of a fraction of MAB-derived cells presenting common properties with satellite muscle stem cells. This analysis also indicated that most cells did not undergo a myogenic differentiation path once in the muscle environment, limiting their capacity to restore dystrophin expression in transplanted muscles. We therefore assessed whether MAB treatment with cytokines and growth factors prior to engraftment may improve their myogenic fate. We identified a combination of such signals that ameliorates MABs capacity to undergo myogenic differentiation in vivo and to restore dystrophin expression upon engraftment in myopathic murine muscles.

KEYWORDS:

Autologous transplantation; Mesoangioblast cells; Muscle dystrophies; Myogenic differentiation; Stem cell fate

PMID:
31683098
DOI:
10.1016/j.scr.2019.101619
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