Genetically engineered mesenchymal stem cells as a proposed therapeutic for huntington's disease

Scott D. Olson, Kari Pollock, Amal Kambal, Whitney Cary, Gaela Marie Mitchell, Jeremy Tempkin, Heather Stewart, Jeannine McGee, Gerhard Bauer, Hyun Sook Kim, Teresa Tempkin, Vicki L Wheelock, Geralyn Annett, Gary Dunbar, Jan Nolta

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

There is much interest in the use of mesenchymal stem cells/marrow stromal cells (MSC) to treat neurodegenerative disorders, in particular those that are fatal and difficult to treat, such as Huntington's disease. MSC present a promising tool for cell therapy and are currently being tested in FDA-approved phase I-III clinical trials for many disorders. In preclinical studies of neurodegenerative disorders, MSC have demonstrated efficacy, when used as delivery vehicles for neural growth factors. A number of investigators have examined the potential benefits of innate MSC-secreted trophic support and augmented growth factors to support injured neurons. These include overexpression of brain-derived neurotrophic factor and glial-derived neurotrophic factor, using genetically engineered MSC as a vehicle to deliver the cytokines directly into the microenvironment. Proposed regenerative approaches to neurological diseases using MSC include cell therapies in which cells are delivered via intracerebral or intrathecal injection. Upon transplantation, MSC in the brain promote endogenous neuronal growth, encourage synaptic connection from damaged neurons, decrease apoptosis, reduce levels of free radicals, and regulate inflammation. These abilities are primarily modulated through paracrine actions. Clinical trials for MSC injection into the central nervous system to treat amyotrophic lateral sclerosis, traumatic brain injury, and stroke are currently ongoing. The current data in support of applying MSC-based cellular therapies to the treatment of Huntington's disease is discussed.

Original languageEnglish (US)
Pages (from-to)87-98
Number of pages12
JournalMolecular Neurobiology
Volume45
Issue number1
DOIs
StatePublished - Feb 2012

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Keywords

  • BDNF
  • Clinical trials
  • Human mesenchymal stem cells
  • Huntington's disease
  • Hypoxia
  • Neurite outgrowth
  • Neurodegenerative diseases
  • Tissue repair

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Olson, S. D., Pollock, K., Kambal, A., Cary, W., Mitchell, G. M., Tempkin, J., Stewart, H., McGee, J., Bauer, G., Kim, H. S., Tempkin, T., Wheelock, V. L., Annett, G., Dunbar, G., & Nolta, J. (2012). Genetically engineered mesenchymal stem cells as a proposed therapeutic for huntington's disease. Molecular Neurobiology, 45(1), 87-98. https://doi.org/10.1007/s12035-011-8219-8