Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal motor neuron disease. Patients have a median survival time of three years upon diagnosis, with gradual loss of motor functions and eventually succumbing to respiratory failure. There is no effective therapy, but recent trials of stem cells transplantation have shown modest benefit to patients, potentially altering the properties of immune cells.
Amyotrophic lateral sclerosis (ALS) is progressive neurodegenerative disease that attacks nerve cells in the brain and spinal cord, causing them to die. When these cells die, a patient will experience loss of movement and voluntary muscle control. In the later stages of the disease, patients are totally paralyzed, but their mind is usually not affected.
There is no effective therapy, and many drugs that showed some promise in animal models have been trialed and failed in humans. Cell-based therapy is another possible option. Perhaps the most readily available autologous transplantation material from an adult human is mesenchymal stem cells (MSCs), which could be obtained and expanded from multiple tissue sources. Recent clinical trials of MSCs transplantation for ALS have demonstrated that the procedure is relatively safe, and there were some very modest indication of benefit to patients.
In a review from Reviews in the Neurosciences, the known, emerging and postulated mechanisms of action underlying beneficial effects that transplanted MSCs may exert to promote motor neuron survival in ALS are discussed. MSCs could provide a range of neurotrophic support for diseased and dying neurons via intercellular transfer of soluble factors, microvesicles and the formation of connecting bridges known as tunneling nanotubes. Perhaps more importantly, MSCs and their secreted factors could modify the disease environment and suppress the detrimental neuroinflammatory condition induced by immune cells and glia cells. They could also help to alter the properties of immune cells that may infiltrated the central nervous system environment as well as reactive glia cells to ones that are more conducive for neuronal survival and growth.
The clinical efficacy of MSC-based therapy could be potentially improved if the mechanisms underlying the beneficial effects of transplanted MSCs are more clearly deciphered in cellular and molecular terms. Novel ways whereby MSCs could act in modifying disease progression in ALS should therefore be actively investigated and delineated. Therapeutic improvements could then be made by augmenting or combining these mechanisms in a strategic manner.
The use of MSCs in cell-based therapy of ALS is reviewed from a cell biological perspective, and the need for further research into the mechanisms involved to drive improvement in efficacy is emphasized.
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