Mesenchymal stem cells for the treatment of neurodegenerative disease

Abstract

Mesenchymal stem cells/marrow stromal cells (MSCs) present a promising tool for cell therapy, and are currently being tested in US FDA-approved clinical trials for myocardial infarction, stroke, meniscus injury, limb ischemia, graft-versus-host disease and autoimmune disorders. They have been extensively tested and proven effective in preclinical studies for these and many other disorders. There is currently a great deal of interest in the use of MSCs to treat neurodegenerative diseases, in particular for those that are fatal and difficult to treat, such as Huntington's disease and amyotrophic lateral sclerosis. Proposed regenerative approaches to neurological diseases using MSCs include cell therapies in which cells are delivered via intracerebral or intrathecal injection. Upon transplantation into the brain, MSCs promote endogenous neuronal growth, decrease apoptosis, reduce levels of free radicals, encourage synaptic connection from damaged neurons and regulate inflammation, primarily through paracrine actions. MSCs transplanted into the brain have been demonstrated to promote functional recovery by producing trophic factors that induce survival and regeneration of host neurons. Therapies will capitalize on the innate trophic support from MSCs or on augmented growth factor support, such as delivering brain-derived neurotrophic factor or glial-derived neurotrophic factor into the brain to support injured neurons, using genetically engineered MSCs as the delivery vehicles. Clinical trials for MSC injection into the CNS 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 are discussed.

Figure 1. Mesenchymal stem cell-mediated neurotrophic factor secretion to promote neuritogenesis and synaptic connection between damaged neurons

(A) Damaged neurons ‘round-up’ and retract axons, this prevents effective signaling between cells in the neural network. (B) Mesenchymal stem cells can promote axon extension to restore synaptic connections between neurons by secreting neurotrophic factors. Additional benefits from mesenchymal stem cells in the brain tissue are reduction in inflammation at sites of damage, increased vascularization, reduction of levels of free radicals and a local reduction in apoptosis of damaged cells.