Mesenchymal Stem Cells for the Treatment of Huntington's Disease

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July 21, 2011

Mesenchymal stem cells/marrow stromal cells (MSC) present a promising tool for cell therapy, and are currently being tested in FDA-approved clinical trials for myocardial infarction, stroke, meniscus injury, limb ischemia, graft-vs.-host disease, autoimmune disorders, and others. The injected stem cells home to the injured area, in particular to hypoxic and/or inflamed areas, and release trophic factors that hasten endogenous repair. These secreted bioactive factors suppress the local immune system, enhance angiogenesis, inhibit fibrosis and apoptosis, and stimulate recruitment, retention, mitosis and differentiation of tissue-residing stem cells. There is currently much interest in the use of MSC to treat neurodegenerative diseases such as Huntington’s disease and Amyotrophic lateral sclerosis. 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, decrease apoptosis, reduce levels of free radicals, encourage synaptic connection from damaged neurons, and regulate inflammation, primarily through paracrine actions. MSC transplanted into the brain have been shown to promote functional recovery by producing trophic factors that induce survival and regeneration of host neurons. Therapies will capitalize upon the innate trophic support from MSC or on augmented growth factor support, such as delivering brain-derived neurotrophic factor (BDNF) or glial-derived neurotrophic factor (GDNF) into the brain to support injured neurons, using genetically engineered MSC as the delivery vehicles. Clinical trials for MSC injection into the central nervous system to treat traumatic brain injury and stroke are currently ongoing. The current data in support of applying MSC-based cellular therapies to the treatment of neurodegenerative disorders will be discussed.

BioengineeringStem Cells

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