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Abstract

Duchenne Muscular Dystrophy (DMD) is a genetic progressive muscle disease resulting from the lack of dystrophin and without effective treatment. Adult stem cell populations have given new impetus to cell-based therapy of neuromuscular diseases. One of them, the Muscle-Derived Stem Cells isolated based on delayed adhesion properties, has been shown to contribute to injured muscle repair. However, these data were collected in dystrophic mice that exhibit a relatively mild tissue phenotype and clinical features of DMD patients.

Here, we characterized canine delayed adherent stem cells and investigated efficacy of their systemic delivery in the clinically relevant DMD animal model to assess potential therapeutic application in Human.

Delayed adherent stem cells, named MuStem cells, were isolated from healthy dog muscle using a preplating technique. In vitro experiments showed that MuStem cells displayed a large expansion capacity, an ability to proliferate in suspension and a multi-lineage differentiation potential. Phenotypically, they corresponded to early myogenic progenitors and uncommitted cells. When injected in immunosuppressed dystrophic dog, they contributed to myofiber regeneration, satellite cell replenishment and dystrophin expression. Importantly, their systemic delivery resulted in long-term dystrophin expression, muscle damage course limitation with an increased regeneration activity and an interstitial expansion restriction, and persisting stabilization of dog’s clinical status.

These results demonstrate that MuStem cells provide an attractive therapeutic avenue for DMD patients.

PhD supervisors: Karl Rouger, Chérel Yan

Partners:

• INSERM UMR 649, Nantes;
• INRA/Oniris UMR IECM, Nantes;
• INSERM ESPRI-EA3855, Tours;
• CNRS UMR 6026, Rennes.

Associated publication:

• Rouger K, Larcher T, Dubreil L, Deschamps JY, Le Guiner C, Jouvion G, Delorme B, Lieubeau B, Carlus M, Fornasari B, Theret M, Orlando P, Ledevin M, Zuber C, Leroux I, Deleau S, Guigand L, Testault I, Le Rumeur E, Fiszman M, Chérel Y. Systemic delivery of allogenic muscle stem cells induces long-term muscle repair and clinical efficacy in duchenne muscular dystrophy dogs. Am J Pathol. 2011 Nov;179(5):2501-18. doi: 10.1016/j.ajpath.2011.07.022.

2008-2011