title: Transplanted modified muscle progenitor cells expressing a mixture of neurotrophic factors delay disease onset and enhance survival in the SOD1 mouse model of ALS.
abstract: Neurotrophic factors (NTFs) are essential growth factor proteins that support the development, survival, and proper function of neurons. We have developed muscle progenitor cell (MPC) populations expressing brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), or insulin-like growth factor-1 (IGF-1). Transplantation of a mixture of such MPC populations (MPC-MIX) into the hind legs of SOD1 G93A transgenic mice (SOD1 mice), the commonly used model of ALS, delayed the onset of disease symptoms by 30 days and prolonged the average lifespan by 13 days. Treated mice also showed a decrease in the degeneration of neuromuscular junction and an increase in axonal survival. Cellular mechanism assays suggest a synergistic rescue effect of NTFs that involves the AKT and BAD signaling pathways. The results suggest that long-term delivery of a mixture of several NTFs by the transplantation of engineered MPC has a beneficial effect in the ALS mouse model.
authors.affiliation: Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Dadon-Nachum
authors.forename: K
authors.initials: K
authors.lastname: Ben-Yaacov
authors.forename: T
authors.initials: T
authors.lastname: Ben-Zur
authors.forename: Y
authors.initials: Y
authors.lastname: Barhum
authors.forename: D
authors.initials: D
authors.lastname: Yaffe
authors.forename: E
authors.initials: E
authors.lastname: Perlson
authors.forename: D
authors.initials: D
authors.lastname: Offen
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D032446:Myoblasts / Q000378:metabolism* / Q000637:transplantation; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: D009414:Nerve Growth Factors; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1