title: Ex Vivo Gene Therapy Using Human Mesenchymal Stem Cells to Deliver Growth Factors in the Skeletal Muscle of a Familial ALS Rat Model.
abstract: Therapeutic protein and molecule delivery to target sites by transplanted human stem cells holds great promise for ex vivo gene therapy. Our group has demonstrated the therapeutic benefits of ex vivo gene therapy targeting the skeletal muscles in a transgenic rat model of familial amyotrophic lateral sclerosis (ALS). We used human mesenchymal stem cells (hMSCs) and genetically modified them to release neuroprotective growth factors such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF). Intramuscular growth factor delivery via hMSCs can enhance neuromuscular innervation and motor neuron survival in a rat model of ALS (SOD1(G93A) transgenic rats). Here, we describe the protocol of ex vivo delivery of growth factors via lentiviral vector-mediated genetic modification of hMSCs and hMSC transplantation into the skeletal muscle of a familial ALS rat model.
authors.affiliation: Department of Comparative Biosciences, The Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, 4124 Veterinary Medicine Building, 2015 Linden Drive, Madison, WI, 53706, USA. msuzuki3@wisc.edu.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
authors.forename: Clive N
authors.initials: CN
authors.lastname: Svendsen
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000628:therapy*; D000818:Animals; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics*; D006801:Humans; D007273:Injections, Intramuscular; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: Amyotrophic lateral sclerosis (ALS ); Cell transplantation; Ex vivo gene therapy; Glial cell line-derived neurotrophic factor (GDNF ); Growth factor s; Human mesenchymal stem cell s; Lentivirus; Vascular endothelial growth factor (VEGF )