PMID: identifiant
de la référence Pubmed : |
 |
 (21924229) |
|
| titre : |
|
Systemic delivery of allogenic muscle stem cells induces long-term muscle repair and clinical efficacy in duchenne muscular dystrophy dogs. |
|
| auteur(s) : |
|
Karl Rouger ( ) 1, 2, Thibaut Larcher1, 2, Laurence Dubreil1, 2, Jack-Yves Deschamps1, 2, Caroline Le Guiner3, 4, Gregory Jouvion5, Bruno Delorme6, 7, Blandine Lieubeau2, 8, Marine Carlus1, 2, Benoît Fornasari1, 2, Marine Theret1, 2, Priscilla Orlando1, 2, Mireille Ledevin1, 2, Céline Zuber1, 2, Isabelle Leroux1, 2, Stéphane Deleau1, 2, Lydie Guigand1, 2, Isabelle Testault9, Elisabeth Le Rumeur10, Marc Fiszman11, Yan Chérel () 1, 2 |
|
| laboratoire : |
|
|
|
| résumé : |
|
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. |
|
| domaine : |
|
|
|
langue du texte
intégral : |
|
Anglais |
|
| ISSN : |
|
0002-9440 |
|
|
| type de publication : |
|
Articles dans des revues avec comité de lecture |
|
| DOI : |
|
10.1016/j.ajpath.2011.07.022 |
|
| journal : |
|
| American Journal of Pathology (Am J Pathol) |
| Publisher |
American Society for Investigative Pathology (ASIP) |
| ISSN |
0002-9440 (eISSN : 1525-2191) |
|
|
| Audience : |
|
internationale |
|
| date de publication : |
|
11/2011 |
|
date de publication
électronique : |
|
13/09/2011 |
|
| volume : |
|
179 |
|
| numéro : |
|
5 |
|
| page, identifiant, ... : |
|
2501-18 |
|
|
| Descripteur(s) MeSH : |
|
Animals – Cell Differentiation – Cell Proliferation – Cells – Cultured – Dogs – Dystrophin – Immunosuppressive Agents – Injections – Intramuscular – Muscle Cells – Muscle – Skeletal – Muscular Dystrophy – Animal – Duchenne – Stem Cell Transplantation – Stem Cells – Transplantation – Homologous |
|
| contrat, financement : |
|
Supported by the Association Française contre les Myopathies (A.F.M.). |
|
