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Ex Vivo Gene Therapy Using Human Mesenchymal Stem Cells to Deliver Growth Factors in the Skeletal Muscle of a Familial ALS Rat Model

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Gene Therapy for Neurological Disorders

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1382))

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 (SOD1G93A 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.

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Acknowledgments

We gratefully acknowledge Ilaria Bellantuono (The University of Sheffield; UK) for providing the GFP-expressing hMSC lines and Patrick Aebischer (Brain & Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Switzerland) for producing lentiviral vectors. We thank Christina Lewis (University of Wisconsin, Madison, WI) for the help in preparing this manuscript and Soshana Svendsen (Cedars-Sinai Medical Center, Los Angeles, CA) for critical review and editing. This work was supported by grants from the ALS Association, NIH (R21NS06104 and R01NS091540 to M.S) and the University of Wisconsin Foundation.

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Authors and Affiliations

  1. 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

    Masatoshi Suzuki

  2. Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA

    Clive N. Svendsen

Authors
  1. Masatoshi Suzuki
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  2. Clive N. Svendsen
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Correspondence to Masatoshi Suzuki .

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Editors and Affiliations

  1. Translational Science and Molecular Medicine, Michigan State University, College of Human Science, Grand Rapids, Michigan, USA

    Fredric P. Manfredsson

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Suzuki, M., Svendsen, C.N. (2016). Ex Vivo Gene Therapy Using Human Mesenchymal Stem Cells to Deliver Growth Factors in the Skeletal Muscle of a Familial ALS Rat Model. In: Manfredsson, F. (eds) Gene Therapy for Neurological Disorders. Methods in Molecular Biology, vol 1382. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3271-9_24

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  • DOI: https://doi.org/10.1007/978-1-4939-3271-9_24

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3270-2

  • Online ISBN: 978-1-4939-3271-9

  • eBook Packages: Springer Protocols

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