title: Adaptive Immune Response Impairs the Efficacy of Autologous Transplantation of Engineered Stem Cells in Dystrophic Dogs.
abstract: Duchenne muscular dystrophy is the most common genetic muscular dystrophy. It is caused by mutations in the dystrophin gene, leading to absence of muscular dystrophin and to progressive degeneration of skeletal muscle. We have demonstrated that the exon skipping method safely and efficiently brings to the expression of a functional dystrophin in dystrophic CD133+ cells injected scid/mdx mice. Golden Retriever muscular dystrophic (GRMD) dogs represent the best preclinical model of Duchenne muscular dystrophy, mimicking the human pathology in genotypic and phenotypic aspects. Here, we assess the capacity of intra-arterial delivered autologous engineered canine CD133+ cells of restoring dystrophin expression in Golden Retriever muscular dystrophy. This is the first demonstration of five-year follow up study, showing initial clinical amelioration followed by stabilization in mild and severe affected Golden Retriever muscular dystrophy dogs. The occurrence of T-cell response in three Golden Retriever muscular dystrophy dogs, consistent with a memory response boosted by the exon skipped-dystrophin protein, suggests an adaptive immune response against dystrophin.
authors: Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Unit of Neurology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Milano, Italy.
authors: Clementina
authors: C
authors: Sitzia
authors: Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Unit of Neurology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Milano, Italy.
authors: Andrea
authors: A
authors: Farini
authors: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
authors: Luciana
authors: L
authors: Jardim
authors: Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Unit of Neurology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Milano, Italy.
authors: Paola
authors: P
authors: Razini
authors: Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Unit of Neurology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Milano, Italy; Ystem s.r.l., Milan, Italy.
authors: Marzia
authors: M
authors: Belicchi
authors: Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Unit of Neurology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Milano, Italy.
authors: Letizia
authors: L
authors: Cassinelli
authors: Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Unit of Neurology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Milano, Italy.
authors: Chiara
authors: C
authors: Villa
authors: Ystem s.r.l., Milan, Italy.
authors: Silvia
authors: S
authors: Erratico
authors: Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Unit of Neurology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Milano, Italy.
authors: Daniele
authors: D
authors: Parolini
authors: Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Unit of Neurology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Milano, Italy.
authors: Pamela
authors: P
authors: Bella
authors: Muscular Dystrophy Research Center (AADM/UNAERP), School of Medicine, University of Ribeirão Preto, Ribeirão Preto-SP, Brazil.
authors: Joao Carlos
authors: JC
authors: da Silva Bizario
authors: Université Versailles St-Quentin, UMR S 1179 Inserm, Montigny-le-Bretonneux, France.
authors: Luis
authors: L
authors: Garcia
authors: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
authors: Marcelo
authors: M
authors: Dias-Baruffi
authors: Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Unit of Neurology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Milano, Italy; Ystem s.r.l., Milan, Italy.
authors: Mirella
authors: M
authors: Meregalli
authors: Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Unit of Neurology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Milano, Italy; Ystem s.r.l., Milan, Italy. Electronic address: yvan.torrente@unimi.it.
authors: Yvan
authors: Y
authors: Torrente
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism*; D056704:Adaptive Immunity; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004285:Dogs; D005500:Follow-Up Studies; D006801:Humans; D009137:Muscular Dystrophy, Animal / Q000276:immunology / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000378:metabolism; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D000071916:AC133 Antigen