Muscle regenerative potential of human MuStem cells after injection into injured tissue

Abstract

After intra-arterial delivery in the dystrophic dog, allogeneic 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 long-term ability to proliferate allowing to generate clinically relevant amount of cells. Cultured hMuStem cells do not express hematopoietic, endothelial or myo-endothelial cell markers and reproducibly correspond to a population of early myogenic-committed progenitors with 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.

PhD supervisors: Karl Rouger, Oumeya Adjali, Marie-Anne Colle

Partners:

• UMRS 974 UPMC-INSERM, FRE 3617 CNRS, AIM, Paris;
• INRA/Oniris UMR IECM, Nantes;
• Macopharma, Mouvaux;
• Service de Chirurgie Infantile, CHU, Nantes;
• Centre de Référence des maladies neuromusculaires Nantes-Angers, Service des Explorations Fonctionnelles, CHU, Nantes;
• Laboratoire de Physiopathologie Animale et Pharmacologie fonctionnelle, Oniris, Nantes.

Associated publication:

• Lorant J, Saury C, Schleder C, Robriquet F, Lieubeau B, Négroni E, Leroux I, Chabrand L, Viau S, Babarit C, Ledevin M, Dubreil L, Hamel A, Magot A, Thorin C, Guevel L, Delorme B, Péréon Y, Butler-Browne G, Mouly V, Rouger K. Skeletal Muscle Regenerative Potential of Human MuStem Cells following Transplantation into Injured Mice Muscle. Mol Ther. 2018 Feb 7;26(2):618-633. doi: 10.1016/j.ymthe.2017.10.013.

2014-2017