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Stem cells are cells that have the ability to divide for indefinite periods in culture and give rise to multiple specialized cell types. They can develop into blood, bone, brain, muscle, skin and other organs.
Stem cells occur naturally, or they can be created from other kinds of cells. Stem cells form during development (embryonic stem cells). They are also present in small numbers in many different tissues (endogenous adult stem cells). Most significantly, stem cells can be created from skin cells (induced pluripotent stem cells, or iPS cells).
iPS cells have emerged in recent years as by far the most significant source of stem cells for ALS research. A simple skin biopsy provides the skin cells (fibroblasts). These cells are treated in a lab dish with a precise cocktail of naturally occurring growth factors that turns back the clock, transforming them back into cells much like those that gave rise to themstem cells.
Embryonic stem cells can be isolated from fertilized embryos less than a week old. Before the development of iPS cells, human embryos were the only source of human stem cells for research or therapeutic development. The ethical issues involved hindered development of this research. Most stem cell research in ALS is currently focused on iPS cells, which are not burdened with these issues.
Stem cells are being used in many laboratories today for research into the causes of and treatments for ALS. Most commonly, iPS cells are converted into motor neurons, the cells affected in ALS. These motor neurons can be grown in a dish and studied to determine how the disease develops. They can also be used to screen for drugs that can alter the disease process. The availability of large numbers of identical neurons, made possible by iPS cells, has dramatically expanded the ability to search for new treatments.
Because iPS cells can be made from skin samples of any person, researchers have begun to make individual cell lines derived from dozens of individuals with ALS. Comparing the motor neurons derived from these cells lines allows them to ask what is common, and what is unique, about each case of ALS, leading to further understanding of the disease process.
Stem cells may also have a role to play in treating the disease. The most likely application may be to use stem cells or cells derived from them to deliver growth factors or protective molecules to motor neurons in the spinal cord. Clinical trials of such stem cell transplants are in the early stages, but appear to be safe.
While the idea of replacing dying motor neurons with new ones derived from stem cells is appealing, there are multiple major hurdles that must be overcome before it is a possibility. Perhaps the most challenging is coaxing the implanted cells to grow the long distances from the spinal cord, where they would be implanted, out to the muscle, where they cause contraction. While work is ongoing to overcome these challenges, it is likely that providing support and protection to surviving neurons represents a more immediate possible form of stem cell therapy.
The presence of endogenous stem cells in the adult brain and spinal cord may provide an alternative to transplantation, eliminating the issues of tissue rejection. If there were a way to stimulate resident stem cells to replace dying cells the limitations of transplantation could be overcome. Small biotech companies are pursuing this direction in the hope of finding therapeutic compounds that will do this. Further research into molecules and genes that govern cell division, migration and specialization is needed, ultimately leading to new drug targets and therapies for ALS.
The mechanism of motor neuron death in ALS remains unclear. It is not certain that transplanted stem cells would be resistant to the same source(s) of damage that causes motor neurons to die and stem cells may need to be modified to protect against the toxic environment. There is also the potential that cultured stem cells used in transplant medicine could face rejection by the body's immune system.
The NeuralStem trial demonstrated the safety of transplanting human embryonic stem cells into the spinal cord of people with ALS. As of late 2014, a larger trial of the same technique is underway, to determine whether treatment can improve function or slow decline. More information can be found here: http://www.alsconsortium.org/news_neuralstem_phaseII_first_patient.php
The BrainStorm trial is underway as of late 2014, examining the safety and efficacy of transplantation of autologous mesenchymal stem cells secreting neurotrophic factors. These stem cells are extracted from the patients own bone marrow, then treated to increase their production of protective factors, and then injected into muscle and the region surrounding the spinal cord. More information can be found here: http://www.alsconsortium.org/
Read The ALS Associations Statement on Stem Cell Research.
Last update: 08/26/14
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