Friday, December 13, 2013

How Do We Fix That Spinal Cord Injury? A Look At Navigating Stem Cells Through Scar Tissue

            Stem cells have become a topic of much debate, both good and bad, within the medical and scientific field. With the start of the new millennium came great new insights into what stem cells are and how they function. The Human Genome Project, completed in 2003, only further developed scientific understanding of DNA, genes, and ultimately stem cells. Many scientists are working to discover the potential of these cells, especially their therapeutic potential. Dr. Hui Ye of Loyola University Chicago is one such scientist who is looking to take these cells and make use of them in the central nervous system (CNS). As a neurobiology professor, he is interested in taking these stem cells and moving them with an electric field so that they migrate to a target area in the body, a process called galvanotaxis. Particularly, he is looking at spinal cord injuries and how to target specific areas of the injury with these stem cells so that the cells can migrate to that area, settle, and differentiate into the desired cell, either neurons or glia. Dr. Ye is hoping that the magnetic field will generate a movement of these cells that is specific and not random as is observable when the stem cells are injected to the target site without being given any particular direction.
            Dr. Ye's former work with rats proved to be somewhat successful by injecting stem cells into an injured spinal cord in order to form oligodendrocytes. These glial cells form myelin sheaths around the neurons that assist in the neuron's conduction of action potentials. Although the injection did help somewhat, the final placement of these cells where not exactly where his research group had hoped the neural precursor cells (NPCs) would settle. The difficulty of getting these cells to go where they should go for the greatest therapeutic effect is caused by scar tissue that builds up and surrounds the injured spot of the spinal cord. This scar tissue is mainly made up of astrocytes, a type of glial cell that performs many functions in the CNS such as providing nutrients to the nervous tissue or maintaining the extracellular ion balance. These astrocytes also play a role in the repair and scarring process after traumatic injury to either the brain or the spinal card by rapidly dividing and filling up the injured site. These glial cells cannot produce action potentials of their own so once these cells produce scar tissue, neurons have difficulty passing signals along to other neurons on the other side of the scar tissue. Also, neurons cannot regrow within the scar tissue preventing the reformation of connections where there were connections before an injury. This scar tissue ultimately prevented the stem cells injected into the rat spinal cords from reaching that area that Dr. Ye's research group was targeting.
            Through the use of galvanotaxis Dr. Ye hopes to be able to navigate the stem cells through the scar tissue and accurately place the stem cells in the correct position so that they can differentiate into whatever cells are necessary to restore connections between neurons, and eventually restore the organism's ability to move. Dr. Ye hopes to discover with his current research whether the cell's movement in an electric field is due to the stem cell's surface charge or the movement of calcium into and out of the cell that promotes actin depolymerization and polymerization respectively (breakdown and growth of cellular molecules that provide structure within the cell), or both! He also hopes to use different conditions in the solution that the stem cells sit in to determine how they will affect the movement of the cells. Such conditions include using different pH levels, using alternating current (AC) instead of direct current (DC) and using calcium channel blockers. The calcium channel blockers should also provide an answer as to whether or not the movement of calcium is what causes the movement of the stem cells in the electric field.
            While navigating through astrocytes is one of Dr. Ye's goals, an article titled "Stem Cell Scarring Aids Recovery from Spinal Cord Injury" from ScienceDaily presents research that claims stem cells already in the spinal cord that normally differentiate into scar tissue could potentially be stimulated to become other cells that could restore function. This research group from Karolinska Institutet in Sweden wanted to see if blocking scar tissue formation by preventing the spinal cord stem cells from forming into scar tissue cells would allow neural regeneration to occur without being blocked. Nevertheless, what they discovered was the complete opposite! By blocking scar tissue formation, what resulted was a gradual expansion of the injury site and more nerves fibres were severed. What they observed in the mice was that mice with blocked stem cell function had more dead nerve cells in the spinal cord than those mice who had normal stem cell function. Thus, it turns out that scar tissue is necessary to prevent further injury to the spinal cord because the scarring "'facilitate[s] the survival of damaged nerve cells'". The researchers determined that more scar tissue limits the consequences of injury. Like Dr. Ye's work, this group acknowledges that injecting stem cells into the site of injury can be beneficial, but they also suggest that stimulation of the spinal cord's own stem cells may provide an alternative that Dr. Ye is not looking at. The stem cells would already be within the injured area, but as to whether or not they would need to be navigated a little to be in the correct position is still unclear. In addition, the next difficulty lies in how to get these stem cells to differentiate into the desired cells once they are in the correct location.

Source:

Karolinska Institutet. "Stem cell scarring aids recovery from spinal cord injury." ScienceDaily,      31 Oct.     2013. Web. 10 Dec. 2013.

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