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

Molecular neurobiology | January 16, 2012 |

Olson, Scott D | Pollock, Kari | Kambal, Amal | Cary, Whitney | Mitchell, Gaela-Marie | Tempkin, Jeremy | Stewart, Heather | McGee, Jeannine | Bauer, Gerhard | Kim, Hyun Sook | Tempkin, Teresa | Wheelock, Vicki | Annett, Geralyn | Dunbar, Gary | Nolta, Jan A
Olson, Pollock, et al. "Genetically engineered mesenchymal stem cells as a proposed therapeutic for Huntington's disease." Molecular neurobiology 45.1 (2012): 87-98. Web.

Abstract

There is much interest in the use of mesenchymal stem cells/marrow stromal cells (MSC) to treat neurodegenerative disorders, in particular those that a ... oke are currently ongoing. The current data in support of applying MSC-based cellular therapies to the treatment of Huntington's disease is discussed.

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.

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12035_2011_8219_fig1_html
Fig 1. Olson, Pollock, et al. "Genetically engineered mesenchymal stem cells as a proposed therapeutic for Huntington's disease." Molecular neurobiology 45.1 (2012): 87-98. Web.
12035_2011_8219_fig1_html
Fig 1. Olson, Pollock, et al. "Genetically engineered mesenchymal stem cells as a proposed therapeutic for Huntington's disease." Molecular neurobiology 45.1 (2012): 87-98. Web.

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12035_2011_8219_fig2_html
Fig 2. Olson, Pollock, et al. "Genetically engineered mesenchymal stem cells as a proposed therapeutic for Huntington's disease." Molecular neurobiology 45.1 (2012): 87-98. Web.
12035_2011_8219_fig2_html
Fig 2. Olson, Pollock, et al. "Genetically engineered mesenchymal stem cells as a proposed therapeutic for Huntington's disease." Molecular neurobiology 45.1 (2012): 87-98. Web.

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