Stem Cell Use in Spinal Cord Injuries

A horrific accident known as a spinal cord injury (SCI) can leave sufferers with a severe handicap that is usually irreversible and affects both their motor and sensory abilities. According to recent studies, there are currently over a million patients who are disabled by paralysis brought on by SCI, with an average of 29.5 cases per million people per year. The disorder affects patients, families, and the entire community in a way that results in significant disability and increased medical expenses. Primary spinal cord injuries can result from a variety of incidents, including car accidents, slips, fights, sports accidents, various work-related injuries, and more. The study shows that young men are the most afflicted with incidences of SCI referring to the age bracket between 20 and 29. Over long period, myriads of treatment approaches have been available to the patients with Spinal cord injury (Nandoe et al. 2012). The remedies included medicinal treatment, surgical operations, and rehabilitative therapies but none of the treatment approaches offered satisfactory help to the patients suffering from chronic level of spinal cord injury.
The study has shown that after Spinal cord injury, various unfortunate environments such as the discharge of inhibitory molecules and establishment of glial scar hampers the recovery process for the patients. Such environment stops the regeneration of axons in the site of injury leading to few options for recovery or even permanent damage. Due to heightened limitations in treatment approaches intensive research has been undertaken into clinical stem cell therapy process to assist in the treatment of the conditions. The use of the stem cells in the treatment of spinal cord injuries is aimed at regenerating essential portions of the injured spinal cord parts (Nandoe et al., 2012).
Treatment of Spinal Cord Injuries from Stem Cells
Stem cells have unique befitting features that allow their inclusion in the regenerative treatment of the spinal cord. Dual characteristics of the stem cells that remarkably distinguish them from other cells is the ability to differentiate into a wide range of cells and their excellent renewability capacity. The stem cells also release essentials substances, for instance, cytokine, growth agents, and trophic factors that enhance neuroprotection. Stem cells show a multiplicity of features based on the characteristic origin and ability to differentiate (Nandoe et al., 2012). Normally, stem cells from embryos are classified as pluripotent due to their capacity to differentiate into three germ layers while the adult stem cells are considered to be multipotent since they comparably have limited capacity to differentiate.
The employment of the stem cell therapy treatments avails multiple benefits, for instance, replacing neuronal cells, corresponding remyelination of axons, restoration of the glial cells, and amplification of trophic molecules. The incorporation of the Stem cells has also been established to promote angiogenesis, offer linkages of cavities, reduction of inflammation, and enhanced excitation of the endogenous precursor cells to enhance the neuronal plasticity. The most common types of stem cells include Schwann cells, Olfactory ensheathing cells, embryonic stem cells and bone marrow derivative mesenchymal stem cells (Muheremu, Peng & Ao, 2016).
Schwann Cells
The Schwann cells are responsible for the support of glia along the peripheral nervous system and are also vital in the production of the myelin sheath for the peripheral axon. The cells act in support of the control bands for the remyelination and axonal renewal following nerve injuries. Implantation of the Schwann cells inside the spinal cord helps in the production of multiple neurotrophic factors that enhance the neuronal survival thus supporting axonal growth. Schwann cells were the initial cells used utilized in the treatment of SCI amongst the animal models with the sole purpose of promoting regeneration of the axon. It was also investigated in numerous preclinical studies of the spinal cord injuries. During research, after injection of Schwann cells into the hollow near the injured spinal cord for the patients with entirely chronic cases of Spinal cord injuries, a follow-up moves portrayed significant levels of progress was observed in the motor and sensory working. Further studies elaborated enhanced safety from the Schwann cells, and there was no detection of the malignant transformation or even subsequent abnormal observations (Nandoe et al., 2012).
Olfactory Ensheathing Cells
Other significant stem cells are Olfactory ensheathing cells otherwise abbreviated as OEC. Studies indicated that neurogenesis perpetually happens in the distal segment of the olfactory nerve hence the Olfactory ensheathing cells can be harvested from the olfactory mucosa which exists around the axons of the olfactory neuron. The OECs have also been established to have the capacity to differentiate into non-olfactory cell kinds; therefore, is a befitting stem cell for conducting stem cell therapy (McDonald et al., 2016). The application in the treatment expedition has not born significant success following some studies. The transplantation of the cells into injured spinal cord did not show significant progress even after further assessment using magnetic resonance image (MRI).
Embryonic Stem Cells
The application of the embryonic stem cells in treatment is also possible. The embryonic stem cells are a hugely pluripotent cell. Therefore, they can differentiate into three primary gem layers which can advance into astrocytes, oligodendrocytes, and even neurons. While the embryonic stem cells hints of better suitability to the use as for stem cell therapy in the Spinal Cord Injury treatment; there are two key challenges. Embryonic stem cells are collected from human embryos and also have the ability to differentiate into malignant transformation cells. Hence the two challenges are ethical nature and unforeseeable practicality due to fears of malignant transformation. Due to the emergence of the probable fears of emergence of teratoma or particularly specified malignancy many clinical studies have reduced in the embryonic stem cells research.
Mesenchymal Stem Cells Collected from the Bone Marrow (Bm Mscs)
The BM MSCs have been established to be multipotent progenitor cells and have the ability to form into Mesodermal types and also induce trophic events that are relatable to the neural cells (Nandoe et al., 2012). The BM MSCs facilitates the protection of the neurons and hence minimizes the reduction of the inflammation and microglial response using the immunosuppressive components. The implantation of BM MSCs causes the filling of the cavity presented by the trauma of the spinal cord and enhances production of the bridging substances. It also expounds the renewal and regeneration of the axon in the cavity. The BM MSCs has also been found to activate the intramedullary endogenous stem cell. The cells can be recovered from the bone marrow, and its use has overcome multiple ethical issues in various societies. The mesenchymal stem cells can also be gathered from the patient's body thus eliminating fears of borrowing cells. The study indicated that in a group of ten patients who underwent spinal cord injury treatment using mesenchymal stem cells, six of them exhibited progress in the motor development of the upper limits (Nandoe et al., 2012).
Types of the Spinal Cord Injuries
The injuries of the Spinal Cord are classified into two main components. They include primary and secondary injuries. Primary damages emanate from multiple occasions such as through exertion of forces, for instance, compression, contusion, tear and many other injuries. The most rampant cause of the injury for the spinal cord is the contusion of the spinal cord due to the fracture or dislocation of the spinal column. After the primary injury, some injuries might emerge. Such injuries are called secondary injuries, and they emerge from the moment of primary injury to multiple weeks after the injury has occurred. When spinal column injury happens, it triggers a chain of events which cascades from edema, reduced flow of blood, vasospasm, production of the free radicals, and inflammation of the injured part. Other events include increased excitotoxicity, peroxidation of the lipids and probable occurrence of ischemia trigger cell apoptosis (Keirstead et al., 2015). Moreover, the astrocytes cause the formation of a glial scar. The glial scar blocks the infiltration of the inflammatory cells and even triggers interference of the regeneration of axon. The presence of cavity attracts fluid which fills the cavity causing the upregulation by the inhibitory molecules which eventually trigger a physical obstacle to regeneration of neurons (Muheremu, Peng & Ao, 2016).
Methods of Maximizing the Therapeutic Impacts of Stem Cell
There are several methodological approaches in the optimization of the therapeutic outcomes from the stem cells. Some of the notable approaches include route of administration and location of injection and appropriate timing of stem cells transplantation process. Another critical issue of concern is the elevation of chances survival and functions of implantation of stem cells (Nandoe et al., 2012).
Route of Administration ad Place of Injection
Proper determination of the desired position for a correct transplantation route of the stem cells is vitally imperative for the satisfactory treatment efficacy. Transplantation of stem cells, quite often happens through use of the direct intramedullary, intravenous and intrathecal forms of injection. In comparison, the intravenous and intrathecal forms of injection are normally less invasive as contrasted to intramedullary injection. The three injection methods apply the homing effect which allows the implanted stem cell to gradually shift to the injured region (Keirstead et al., 2015). The study indicates that intrathecal injection is contrastingly more effectual in animals, for instance, in stem cell engraftment in comparison to the intravenous injection. The report also indicates that holding of intrathecal injection requires relatively large amounts of stem cell numbers to successful access the damaged spinal cord with satisfying amounts of cells. The actions of subarachnoid adhesion may continuously act in resisting the reach of the stem cells to the target site (Wrathall & Lytle, 2012).
In prolonged cases of spinal cord injury whereby the wound-healing process stops, the homing effect also stops thus allowing the application of the stem cells through direct injection (Cummings et al., 2012). Direct injection may cause possible leakage of the cerebrospinal and eventual hemorrhage of the intramedullary. To undertake intramedullary injection successfully it is imperative to analyze the point of injection for the implanting the stem cells. Proximal spinal cord region slightly above the damaged place is the best section for injection to enhance the survival of stem cells; however, caution be observed to inject measured capacity of stem cells as pressure may result in further damage of normal spinal cord (Wrathall & Lytle, 2012).
It is an accepted practice to inject an adequate amount of MSCs into the hollow at the injured region, but the region is considered unreceptive and hostile region for the existence of MSCs due to diminished vascular perfusion. The eventual injection into the contused cavity promotes the resolution of glial scars and also enhances the bridging for axonal renewal. Subsequent research has advocated for the injection of the MSCs in the adjacent region of the injury and also in the point of injury to capture the two groups of merits collected from the two categories. Apart from the intramedullary injection, researchers introduced additional subdural stem cells to enhance the cell numbers hoping that subdural stem cells could move into the spinal cord through the homing effect which may be emanating from the advancement of the intramedullary injection (Muheremu, Peng & Ao, 2016).
Proper Time of Stem Cells Transplantation
In the spinal cord injury, the first three days after the injury are recognized as the acute phase but when the injury last more than 12 months, the period is recognized as chronic phase. The subacute phase falls in between the two phases of chronic and acute. Normally, the process of quick recovery is usually within the first three months which nearly stagnates at the attaining of 12 months of the spinal cord injury. When an injury happens in the spinal cord, multiple secondary injuries occur cascading along due to the presence of the free reactive oxygen radical, the presence of excitatory transmitters, and lastly, inputs of the inflammatory molecules release cytotoxic ambiance for the stem cells implanted in the region. Hypoperfusion causes Hypoxic states, which creates a comparably hostile atmosphere for the introduced stem cells (Nandoe et al., 2012). During the chronic phases, the occurrence of glial scar tissue functions as the physical blockade that impedes the axonal regrowth hence there are few cases of axonal growth during the stages of the chronic phase in contrast to acute or even subacute phases.
Tools of Measuring the Success of Stem Cell Therapy
The main tools are expansively known in the measurement of success or improvement of stem cell therapy. They include electrophysiological (EP) studies, diagnostic imaging study and lastly neurological examination and evaluation for the daily activities of the living organisms (ADL). ADL is the elemental method of assessing the neurologic recovery and includes measurement of the strength of every joint in an objective model. The measurement has international standards adopted for the practice. Electrophysiological findings such as the somatosensory can be taken to identify the potentials and assessment of the effect of stem cell treatments. In many types of research on electrophysiological studies, there was a demonstration of the close affinity between regrowth of neurons and EP change following the stem cell therapy. Diagnostic imaging investigation is normally conducted through approaches such as MRI before and even after stem therapies. The images show changes in the recovery process (Nandoe et al., 2012).
Conclusion
In brief, several research have exposed multiple clinical and experimental findings exhibiting the positive outcomes of the functional enhancement using stem cell treatment methods in the spinal injuries. The precise mechanism of operation of the stem cells still appears not conclusively explored due to the presence of some limitations and vagueness in the stem cell sector. Research should be undertaken to highlight more merits from the stem cell renewal process. Some essential research segments into Human Spinal Cord injury segment faces multiple oppositions from the society. The initial challenge is that SCI is considered very heterogeneous in cause and severity. There are palpable complications in randomization and control trial of the stem cells experiments. Vivid contrast between treatment and associated control group is usually difficult due to the ethical aspects. In some cases, safety and efficiency become an issue since experiments of animals may not directly apply to the humans directly.













References
Nandoe Tewarie, R. S., Hurtado, A., Bartels, R. H., Grotenhuis, A., & Oudega, M. (2012). Stem cell-based therapies for spinal cord injury. The journal of spinal cord medicine, 32(2), 105-114.
Muheremu, A., Peng, J., & Ao, Q. (2016). Stem cell based therapies for spinal cord injury. Tissue and Cell, 48(4), 328-333.
Keirstead, H. S., Nistor, G., Bernal, G., Totoiu, M., Cloutier, F., Sharp, K., & Steward, O. (2015). Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. Journal of Neuroscience, 25(19), 4694-4705.
Wrathall, J. R., & Lytle, J. M. (2012). Stem cells in spinal cord injury. Disease markers, 24(4-5), 239-250.
McDonald, J. W., Liu, X. Z., Qu, Y., Liu, S., Mickey, S. K., Turetsky, D., ... & Choi, D. W. (2016). Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nature medicine, 5(12), 1410-1412.
Cummings, B. J., Uchida, N., Tamaki, S. J., Salazar, D. L., Hooshmand, M., Summers, R., ... & Anderson, A. J. (2012). Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice. Proceedings of the National Academy of Sciences of the United States of America, 102(39), 14069-14074.