Title: Stem cell-based growth factor delivery targeting skeletal muscles as a possible therapy for amyotrophic lateral sclerosis (ALS).
Legend: Human mesenchymal stem cells (hMSCs) are genetically modified by lentiviral infection to release growth factors such as glial cell line-derived neurotrophic factor (GDNF). These cells can be used to deliver growth factors following intramuscular transplantation in a familial ALS rat model. An hMSC line pre-labeled with green fluorescence protein (GFP) has been used for our studies.
Van Dyke JM, Smit-Oistad IM, Macrandar C, Krakora D, Meyer MG, Suzuki M. (2016). Macrophage-mediated inflammation and glial response in the skeletal muscle of a rat model of familial amyotrophic lateral sclerosis (ALS). Experimental Neurology, 277: 275-282.
Suzuki M, Svendsen CN. Ex vivo delivery of growth factors using human mesenchymal stem cells in the skeletal muscle of a familial ALS rat model. (2015). Gene Therapy for Neurological Disorders (ed. F.P. Manfredsson), Methods in Molecular Biology, 1382: 325-36, Humana Press-Springer.
Krakora D, Mulcrone PL, Meyer M, Lewis CM, Bernau K, Gowing G, Zimprich C, Aebischer P, Svendsen CN, Suzuki M. (2013). Synergistic effects of GDNF and VEGF on lifespan and disease progression in a familial ALS rat model. Molecular Therapy, 21: 1602-10.
Suzuki M, McHugh J, Tork C, Shelley B, Hayes A, Bellantuono I, Aebischer P, Svendsen CN (2008). Direct muscle delivery of GDNF with human mesenchymal stem cells improves motor neuron survival and function in a rat model of familial ALS. Molecular Therapy, 16: 2002-10.
Description: Our current research is to apply stem cell technology to disease modeling and therapeutic applications for neuromuscular diseases such as ALS (also known as Lou Gehrig’s disease). ALS causes motor neuron degeneration, muscular atrophy, and ultimately death by respiratory failure. Because ALS is a devastating disease with no effective treatments and no known cures, novel treatments are greatly needed. ALS is an ideal candidate for novel gene and cell therapy approaches as it is both incurable and terminal.
About the Lab: Our group has demonstrated the therapeutic benefits of ex vivo gene therapy (stem cell-based growth/trophic factor delivery) targeting the skeletal muscle to prevent degeneration of motor neurons and associated neuromuscular junctions during ALS. Although most ALS research has focused on mechanisms of motor neuron cell death, degeneration is also observed in skeletal muscle, particularly at the neuromuscular connection. Glial cell line-derived neurotrophic factor and vascular endothelial growth factor (VEGF) promote survival of motor neurons and their neuromuscular junctions in neuromuscular disorders such as ALS. Most recently, we delivered a combination of GDNF and/or VEGF to muscles using hMSCs; the hMSCs survive and synthesize and release growth factors, which slow disease progression in familial ALS model rats.