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.

Bone Marrow-Derived Endothelial Progenitor Cells Protect Postischemic Axons after Traumatic Brain Injury

“…Similarly, mesenchymal stem cells have also been shown to have very poor grafting abilities. 37 Despite a lack of presence in the injured brain, the observed positive effects on white matter in vivo in conjunction with our in vitro data support the notion that posttraumatic EPC activity primarily involves localized release of trophic factors and cytokines.…”

The Regenerative Medicine Laboratory: Facilitating Stem Cell Therapy for Equine Disease

“…[65]. Other diseases in which conventional immunosuppressive therapies fail may provide a rationale for the use of MSC-based therapeutic approaches [66][67][68]. MSC infusions may also play an important role in regulating inflammatory diseases of the central nervous system, although their interactions with the blood brain barrier have not been fully elucidated [67,69,70].…”

Stem cells: novel players in the treatment of erectile dysfunction

“…26 MSCs have been extensively tested and proven effective in preclinical studies, and they currently are being tested in US FDAapproved clinical trials for the treatment of myocardial infarction, stroke, meniscus injury, limb ischemia, graft-versus-host disease and autoimmune disorders. 29 Although the mechanisms are not completely clear, MSCs are known to secrete a broad range of cytokines and growth factors that have both paracrine and autocrine effects on damaged tissues. MSCs have been isolated from bone marrow, adipose tissue, skeletal muscle, dental pulp and cord blood.…”