title: Symptomatic improvement, increased life-span and sustained cell homing in amyotrophic lateral sclerosis after transplantation of human umbilical cord blood cells genetically modified with adeno-viral vectors expressing a neuro-protective factor and a neural cell adhesion molecule.
abstract: Amyotrophic lateral sclerosis (ALS) is an incurable, chronic, fatal neuro-degenerative disease characterized by progressive loss of moto-neurons and paralysis of skeletal muscles. Reactivating dysfunctional areas is under earnest investigation utilizing various approaches. Here we present an innovative gene-cell construct aimed at reviving inert structure and function. Human umbilical cord blood cells (hUCBCs) transduced with adeno-viral vectors encoding human VEGF, GDNF and/or NCAM genes were transplanted into transgenic ALS mice models. Significant improvement in behavioral performance (open-field and grip-strength tests), as well as increased life-span was observed in rodents treated with NCAM-VEGF or NCAM-GDNF co-transfected cells. Active trans-gene expression was found in the spinal cord of ALS mice 10 weeks after delivering genetically modified hUCBCs, and cells were detectable even 5 months following transplantation. Our gene-cell therapy model yielded prominent symptomatic control and prolonged life-time in ALS. Incredible survivability of xeno-transpanted cells was also observed without any immune-suppression. These results suggest that engineered hUCBCs may offer effective gene-cell therapy in ALS.
authors.forename: Rustem Robertovich
authors.initials: RR
authors.lastname: Islamov
authors.forename: Albert Anatolyevich
authors.initials: AA
authors.lastname: Rizvanov
authors.forename: Marat Alexandrovich
authors.initials: MA
authors.lastname: Mukhamedyarov
authors.forename: Ilnur Ildusovich
authors.initials: II
authors.lastname: Salafutdinov
authors.forename: Ekaterina Evgenevna
authors.initials: EE
authors.lastname: Garanina
authors.forename: Valeria Yuryevna
authors.initials: VY
authors.lastname: Fedotova
authors.forename: Valeria Vladimirovna
authors.initials: VV
authors.lastname: Solovyeva
authors.forename: Yana Olegovna
authors.initials: YO
authors.lastname: Mukhamedshina
authors.forename: Zufar Zufarovich
authors.initials: ZZ
authors.lastname: Safiullov
authors.forename: Andrey Alexandrovich
authors.initials: AA
authors.lastname: Izmailov
authors.forename: Daria Sergeevna
authors.initials: DS
authors.lastname: Guseva
authors.forename: Andrey Lvovich
authors.initials: AL
authors.lastname: Zefirov
authors.forename: Andrey Pavlovich
authors.initials: AP
authors.lastname: Kiyasov
authors.affiliation: Department of Medical Biology and Genetics, Kazan State Medical University, ul. Butlerova 49, R- 420012 Kazan, Russia. islamru@yahoo.com.
authors.forename: Andras
authors.initials: A
authors.lastname: Palotas
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D017690:Cell Transplantation; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D008017:Life Expectancy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019006:Neural Cell Adhesion Molecules / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D019006:Neural Cell Adhesion Molecules; D042461:Vascular Endothelial Growth Factor A