Skeletal Muscle Regenerative Potential of Human MuStem Cells following Transplantation into Injured Mice Muscle

After intra-arterial delivery in the dystrophic dog, allogeneic muscle-derived stem cells, termed MuStem cells, contribute to long-term stabilization of the clinical status and preservation of the muscle regenerative process. However, it remains unknown whether the human counterpart could be identif...

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Bibliographic Details
Published in:Molecular therapy 2018-02, Vol.26 (2), p.618-633
Main Authors: Lorant, Judith, Saury, Charlotte, Schleder, Cindy, Robriquet, Florence, Lieubeau, Blandine, Négroni, Elisa, Leroux, Isabelle, Chabrand, Lucie, Viau, Sabrina, Babarit, Candice, Ledevin, Mireille, Dubreil, Laurence, Hamel, Antoine, Magot, Armelle, Thorin, Chantal, Guevel, Laëtitia, Delorme, Bruno, Péréon, Yann, Butler-Browne, Gillian, Mouly, Vincent, Rouger, Karl
Format: Article
Language:English
Subjects:
Adult Stem Cells
Animals
Bone marrow
Cell Differentiation
Cell Proliferation
cell therapy
Cells, Cultured
Clinical trials
Data analysis
Divergence
DMD
Dogs
Endothelial cells
Experiments
Hemopoiesis
human adult stem cells
Humans
Immunodeficiency
Life Sciences
Mesenchyme
Mice
Muscle Development
Muscle function
Muscle, Skeletal - physiology
Muscular dystrophy
Muscular Dystrophy, Animal - therapy
Muscular Dystrophy, Duchenne - therapy
Musculoskeletal system
MuStem
Myoblasts, Skeletal - cytology
Myoblasts, Skeletal - transplantation
Myogenesis
Original
Patients
Preservation
Regeneration
Regenerative Medicine
Rodents
Skeletal muscle
Stem Cell Transplantation
Stem cells
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Summary:After intra-arterial delivery in the dystrophic dog, allogeneic muscle-derived stem cells, termed MuStem cells, contribute to long-term stabilization of the clinical status and preservation of the muscle regenerative process. However, it remains unknown whether the human counterpart could be identified, considering recent demonstrations of divergent features between species for several somatic stem cells. Here, we report that MuStem cells reside in human skeletal muscle and display a long-term ability to proliferate, allowing generation of a clinically relevant amount of cells. Cultured human MuStem (hMuStem) cells do not express hematopoietic, endothelial, or myo-endothelial cell markers and reproducibly correspond to a population of early myogenic-committed progenitors with a perivascular/mesenchymal phenotypic signature, revealing a blood vessel wall origin. Importantly, they exhibit both myogenesis in vitro and skeletal muscle regeneration after intramuscular delivery into immunodeficient host mice. Together, our findings provide new insights supporting the notion that hMuStem cells could represent an interesting therapeutic candidate for dystrophic patients. Rouger et al. show that stem cells termed MuStem reside in healthy human muscle. Following delivery into injured mouse muscle, these early myogenic-committed cells, characterized by a perivascular/mesenchymal signature, give rise to efficient myofiber regeneration, the intensity of which correlates with CD56+ expression. These findings suggest new therapeutic options for muscular dystrophies.
ISSN:1525-0016
1525-0024
DOI:10.1016/j.ymthe.2017.10.013