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Use of Genetically Modified Mesenchymal Stem Cells to Treat Neurodegenerative Diseases
Authors:Robert D Wyse  Gary L Dunbar  Julien Rossignol
Affiliation:1.Field Neurosciences Institute Laboratory for Restorative Neurology, Brain Research and Integrative Neuroscience Center, Program in Neuroscience, Central Michigan University, Mount Pleasant, MI 48859, USA; E-Mails: (R.D.W.); (G.L.D.);2.Field Neurosciences Institute, Saginaw, MI 48604, USA;3.College of Medicine, Central Michigan University, Mt. Pleasant, MI 48859, USA
Abstract:The transplantation of mesenchymal stem cells (MSCs) for treating neurodegenerative disorders has received growing attention recently because these cells are readily available, easily expanded in culture, and when transplanted, survive for relatively long periods of time. Given that such transplants have been shown to be safe in a variety of applications, in addition to recent findings that MSCs have useful immunomodulatory and chemotactic properties, the use of these cells as vehicles for delivering or producing beneficial proteins for therapeutic purposes has been the focus of several labs. In our lab, the use of genetic modified MSCs to release neurotrophic factors for the treatment of neurodegenerative diseases is of particular interest. Specifically, glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and brain derived neurotrophic factor (BDNF) have been recognized as therapeutic trophic factors for Parkinson’s, Alzheimer’s and Huntington’s diseases, respectively. The aim of this literature review is to provide insights into: (1) the inherent properties of MSCs as a platform for neurotrophic factor delivery; (2) the molecular tools available for genetic manipulation of MSCs; (3) the rationale for utilizing various neurotrophic factors for particular neurodegenerative diseases; and (4) the clinical challenges of utilizing genetically modified MSCs.
Keywords:mesenchymal stem cells  genetic engineering  Parkinson’  s  Alzheimer’  s  Huntington’  s  neurodegenerative diseases  transplantation  glial cell-derived neurotrophic factor (GDNF)  brain derived neurotrophic factor (BDNF)  nerve growth factor (NGF)
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