Spinal Cord Injury Treatment with Stem Cells
The central nervous system is formed by the brain and the spinal cord and damage to either one can severely impact movement, sensation, and normal reflexes. The peripheral nervous system (PNS) is that made up by the nerves that branch off from the spinal cord into the rest of the body and some of the nerve signals received from the PNS and conveyed by the PNS never actually reach the brain but are processed instead in the spinal cord. Spinal cord injury is a central nervous system injury and can occur anywhere from the tailbone to the neck, with the most severe and extensive symptoms seen the higher up the injury. The part of the nerve cells that extends through the spinal cord is called the axon and these can be several feet long, but miniscule in diameter. These axons are protected by a fatty substance called myelin which acts as an electrical insulator so that nerve signals remain efficient and strong. Some demyelinating diseases such as multiple sclerosis lead to symptoms of poor motor control and sensation due to the inability of the body to send nerve signals correctly and the same can happen if a spinal cord injury damages the myelin around the axons.
Nerve Cell Regrowth with Stem Cells
The severance of peripheral nerve fibers is not always permanent as the nerve cell can slowly grow back if insulated by the myelin. Where spinal cord injury occurs and many nerve fiber bundles are severed this can create further inflammation and scarring which may then damage surrounding nerves that were not damaged in the initial injury. An initial ‘incomplete’ injury may then worsen as the other nerve fibers progressively deteriorate due to compression. Treatments for spinal cord injury often focus on reducing this initial inflammation and preventing the condition worsening.
Types of Nerve Stem Cells
The nerve fibers in the spinal cord include a number of different types of neural cells and glial cells. The neural cells are those which relay nerve signals by electrical impulse, whereas the glia are those cells which support the neural cells and include oligodendrocytes and astrocytes. Much of the research into spinal cord injury has concentrated on these supportive cells as oligodendrocytes make myelin and astrocytes provide the correct environment for neurons to grow. Neural stem cells have been identified in the central nervous system and are able to aid repair of damaged tissues to some degree which is the suspected mechanism behind the spontaneous recovery sometimes observed in those patients with partial spinal cord lesions. Acute and severe trauma however has rarely resulted in spontaneous functional recovery as the body is likely overwhelmed by the restorative process required. Researchers hopeful of treating spinal cord injury with neural stem cells face a challenge however as, although the stem cells do appear to migrate to the site of injury this only results in the creation of astrocytes and not oligodendrocytes. Without the protective myelin sheath around the nerves the communication network in the central nervous system remains disconnected.
Successful Neural Stem Cell Differentiation
The challenge for scientists then became developing a thorough understanding of the signalling processes behind the differentiation of neural stem cells into specific types of neural cell. With embryonic stem cell research held up for many years by a lack of federal funding in the US, the task has fallen in large part to private companies, such as Geron, to develop stem cell technologies which allowed them to control the differentiation and proliferation of stem cells. Embryonic stem cell research involved looking at the development of individual cell types during early growth and led to a wealth of knowledge regarding the presence of different chemicals and how they influenced cellular differentiation. Researchers have now developed the ability to create neurons and glial cells from embryonic stem cells, and then to create oligodendrocytes. Having a ready source of oligodendrocytes has allowed researchers to test the potential for these myelin-restoring cells to reconnect the brain and the body. It is also possible that induced pluripotent adult stem cells (iPSCs) may also be able to be manipulated into creating oligodendrocytes for autologous stem cell transplants with little risk of immune system rejection (with the exception of diseases such as multiple sclerosis where an autoimmune demyelinating mechanism is suspected).
Skin Stem Cells for Neurological Injury
Researchers in Canada are currently looking at the possibility of using skin-derived stem cells to treat neurological injury and have had some success at creating Shwann cells which are able to guide nerve fibers across an injury site and regenerate myelin to insulate these cells (Biernaskie and Miller, 2010). Miller, et al (2011), have also developed a novel way of tracking myelination using near infra-red fluorescent imaging which will be of considerable use in monitoring treatment progress when histological post-mortem examination is not possible, such as in human trials rather than sacrificial animal trials. Other research using olfactory-ensheathing stem cells to help guide regrowing axons across the injury site is also underway in a number of countries, including China, the US, Australia, and the UK.
Stem Cell Treatment Improved Mobility in Injured Animals
Stem cells differentiated into myelin-producing oligodendrocytes have been shown in animal models to promote locomotor improvements, with some researchers actually using specially selected fetal neural stem cells which preferentially give rise to oligodendrocytes with some success (Salazar, et al, 2010). Exogenous repair is the term given to the technique used by Salazar whereby partially differentiated embryonic stem cells are injected and then the further differentiation into the desired cells is reliant on signals from surrounding cells. Endogenous repair is where stem cells already differentiated into the desired cell type in the laboratory are directly transplanted into the site of injury. FDA-approved clinical trials are now underway in human patients with acute spinal cord injury in order to assess safety, with hope that further developments in the laboratory in the meantime will allow even more clinical trials to be carried out in human patients over the coming years.
Find Out More –> Human Clinical Trials for Stem Cells and Spinal Cord Injury
