Premature proliferative arrest of cricopharyngeal myoblasts in oculo-pharyngeal muscular dystrophy: Therapeutic perspectives of autologous myoblast transplantation |
| |
| Authors: | Périé Sophie Mamchaoui Kamel Mouly Vincent Blot Stéphane Bouazza Belaïd Thornell Lars-Eric St Guily Jean Lacau Butler-Browne Gillian |
| |
| Institution: | 1. Inserm U787 “Groupe Myologie” and Institut de Myologie, Faculté de Médecine Pitié Salpêtrière, Université Paris VI Pierre et Marie Curie, 105, Boulevard de l’Hôpital, 75013 Paris, France;2. Service d’Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale, Faculté de Médecine Saint Antoine, Université Paris VI Pierre et Marie Curie, Hôpital Tenon 4, rue de la Chine, 75020 Paris, France;3. Laboratoire de Neurobiologie, Ecole Vétérinaire d’Alfort 7, avenue du Général de Gaulle 94700 Maisons-Alfort, France;4. Department of Integrative Medical Biology, Section for Anatomy and Center for Musculoskeletal Research, National Institute of Working Life, S-901 and S-907 13 UMEA, Sweden;3. From the MitoCare Center for Imaging Research and Diagnostics, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107,;4. Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, and;5. Division of Clinical and Metabolic Genetics, Hospital for Sick Children and Department of Paediatrics, University of Toronto, Toronto, Ontario M5G 1X8, Canada;1. The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, PR China;2. Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, PR China;3. From the Departments of Physiology, Baltimore, Maryland 21205;5. Departments of Biological Chemistry, Baltimore, Maryland 21205;6. Cell Biology Johns Hopkins University School of Medicine, Baltimore, Maryland 21205,;4. the Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon 97239,;12. the Section on Translational Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892;1. Department of Cardiology, Hunan Provincial People''s Hospital, Changsha, 410005, China;2. Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA |
| |
| Abstract: | Cultures of myoblasts isolated from cricopharyngeal muscles from patients with oculopharyngeal muscular dystrophy (OPMD) have been performed to study the effect of the expanded (GCG)8-13 repeat, located on the poly(A) binding protein nuclear-1 (PABPN1), on satellite cell phenotype. Cell cultures exhibited a reduced myogenicity, as well as a rapid decrease in proliferative lifespan, as compared to controls. The incorporation of BrdU decreased during the proliferative lifespan, due to a progressive accumulation of non-dividing cells. A lower fusion index was also observed, but myoblasts were able to form large myotubes when OPMD cultures were purified, although a rapid loss of myogenicity during successive passages was also observed. Myoblasts isolated from unaffected muscles did not show the defects observed in cricopharyngeal muscle cultures. The PABPN1 was predominantly located in nuclei of myoblasts and in both the nuclei and cytoplasm of myotubes in OPMD cultures. In vivo analysis of OPMD muscles showed that the number of satellite cells was slightly higher than that observed in age matched controls. Mutation of the PABPN1 in OPMD provokes premature senescence in dividing myoblasts, that may be due to intranuclear toxic aggregates. These results suggest that myoblast autografts, isolated from unaffected muscles, and injected into the dystrophic pharyngeal muscles, may be a useful therapeutic strategy to restore muscular function. Its tolerance and feasibility has been preclinically demonstrated in the dog. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ |
|
