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© Research
Publication : The American journal of pathology

Systemic delivery of allogenic muscle stem cells induces long-term muscle repair and clinical efficacy in duchenne muscular dystrophy dogs

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The American journal of pathology - 13 Sep 2011

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

Link to Pubmed [PMID] – 21924229

Am. J. Pathol. 2011 Nov;179(5):2501-18

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, muscle-derived stem cells, isolated based on delayed adhesion properties, contributes 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 the efficacy of their systemic delivery in the clinically relevant DMD animal model to assess potential therapeutic application in humans. Delayed adherent stem cells, named MuStem cells (muscle stem cells), were isolated from healthy dog muscle using a preplating technique. In vitro, MuStem cells displayed a large expansion capacity, an ability to proliferate in suspension, and a multilineage differentiation potential. Phenotypically, they corresponded to early myogenic progenitors and uncommitted cells. When injected in immunosuppressed dystrophic dogs, 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 the dog’s clinical status. These results demonstrate that MuStem cells could provide an attractive therapeutic avenue for DMD patients.