A spinal cord injury can damage a few, many, or almost all of the nerve fibers that cross the site of injury. A variety of cells located in and around the injury site may also die.
Some injuries having little or no nerve cell death may allow an almost complete recovery. Primary damage is immediate and is caused directly by the injury. Secondary damage results from inflammation and swelling that can press on the spinal cord and vertebrae, as well as from changes in the activity of cells and cell death. Motor vehicle accidents and catastrophic falls are the most common causes of SCI in the United States.
The rest are due to acts of violence primarily gunshot wounds and assaults , sports injuries, medical or surgical injury, industrial accidents, diseases and conditions that can damage the spinal cord, and other less common causes. For information on what makes up the spinal cord and spinal column, see the Appendix at the end of this document. The emergency room physician will check for movement or sensation at or below the level of injury, as well as proper breathing, responsiveness, and weakness.
Emergency medical tests for a spinal cord injury include:. At the accident scene , emergency personnel will put a rigid collar around the neck and carefully place the person on a rigid backboard to prevent further damage to the spinal cord. Sometimes the person may be sedated to relax and prevent movement. Once someone has survived the injury and begins to cope psychologically and emotionally, the next concern is how to live with disabilities.
Doctors are now able to predict with reasonable accuracy the likely long-term outcome of spinal cord injuries. This helps people experiencing SCI set achievable goals for themselves and gives families and loved ones a realistic set of expectations for the future. Rehabilitation programs combine physical therapies with skill-building activities and counseling to provide social and emotional support, as well as to increase independence and quality of life.
A rehabilitation team is usually led by a doctor specializing in physical medicine and rehabilitation called a physiatrist and often includes social workers, physical and occupational therapists, recreational therapists, rehabilitation nurses, rehabilitation psychologists, vocational counselors, nutritionists, a case worker, and other specialists.
In the initial phase of rehabilitation, therapists emphasize regaining communication skills and leg and arm strength. For some individuals, mobility will only be possible with assistive devices such as a walker, leg braces, or a wheelchair. Communication skills such as writing, typing, and using the telephone may also require adaptive devices for some people with tetraplegia.
However, by definition, ESCs need to be harvested from embryonic cells, which raises significant ethical issues. Geron Corporation launched a phase I clinical trial of a human ESC-based therapy for SCI in , but announced that they will discontinue the clinical trial after transplanting four of the planned 10 patients, ostensibly due to financial considerations, and the results of this trial have not been released.
OPC produces neurotrophic factors, stimulates microvasculature re-vascularization, and promotes the remyelination of denuded axons, which are critical for axon regeneration [ , ]. The results had not yet been released at the time of publication. Cell dose is among the most important clinical variables; however, it is difficult to determine the optimal dose in humans from the results of animal experiments because of the differences in body weight and spinal cord size.
Based on our review of clinical trials, cell doses vary widely among trials, ranging from 10 6 to 10 10 cells. The application routes can be divided into intra-arterial, intravenous, intrathecal, and intraspinal, with the results of animal experiments comparing the efficacy of each route shown in Table 2 [ , , , , ]. Intravenous transplantation has the advantage of the lowest invasiveness, which enables multiple injections without special equipment.
However, despite its efficacy, small amounts of cells are often found in the damaged lesion when this method is used. The intra-arterial approach is superior to intravenous administration in delivering more cells to the lesion; however, ischemic damage caused by cell clusters clogging the artery needs to be avoided.
Intrathecal application can also deliver a large number of cells to the spinal cord and is less invasive relative to intraspinal application; however, the rate of cell engraftment is unclear, and complications, such as hydrocephalus and liquorrhea, need to be addressed. The intraspinal approach of direct cell administration achieves the highest level of cell engraftment but requires invasive surgery, and the risk of additional SCI being caused by injection needles should not be underestimated.
The ASIA impairment scale is the most frequently used metric for determining study inclusion, and often, only patients with the ASIA A impairment level complete motor and sensory loss below the level of injury are included in the trials. There are several outcome measures adopted by the clinical trials, with the most frequent being the change in the ASIA scale classification.
Arguably, the most meaningful outcome measure is yet to be determined. Recent clinical trials launched by companies are seldom completed before early results indicate a failure to meet expectations. The results of these terminated trials are then not reported because they are not deemed beneficial to the funding company [ 42 ].
Aside from the large number of experimental studies, clinical trials associated with SCI remains in its infancy. Although the results are somewhat promising, the establishment of the most effective treatment strategies, including cell type, dose, route, and timing, is yet to be realized.
One pitfall that should be emphasized is that most of these clinical trials are single-centered, investigator-oriented trials. Clinical trials aiming to obtain drug approval are more highly restrictive and include external monitoring to assure good laboratory practices, good clinical practices, and good manufacturing practices established for each country.
However, these procedures are often very expensive and differ between countries, which increase the trial threshold for clinical trials. The standardization of the regulations between agencies, such as the United States Food and Drug Administration and the European Medicines Agency, is warranted.
The heterogeneous results of clinical trials using stem cells for SCI treatment suggest a need for further assessment and basic experimentation. The biggest movement of clinical trials is that the trials are moving from investigator-oriented academic research to profit-oriented, company-funded research.
The results of the studies, as well as their cost effectiveness, will be key to the future development of stem cell research. Conceptualization, M. All authors have read and agreed to the published version of the manuscript. National Center for Biotechnology Information , U.
Int J Mol Sci. Published online Jun 2. Author information Article notes Copyright and License information Disclaimer. Received Apr 26; Accepted May This article has been cited by other articles in PMC.
Abstract There are more than one million patients worldwide suffering paralysis caused by spinal cord injury SCI. Keywords: stem cell, spinal cord injury, neurogenesis, inflammation, regenerative medicine, transplantation.
Introduction Spinal cord injury SCI is mainly caused by severe trauma from traffic accidents, falls, and sports-related injuries, and there are more than one million patients worldwide suffering from SCI-related paralysis. Open in a separate window. Figure 1. Figure 2. Mechanisms of Action of Stem Cell Transplantation Extensive efforts have been applied to elucidate the mode of action of stem cell transplantation in treating SCI, and multiple descriptive reviews have been published [ 61 , 62 ].
Key Segment of Clinical Trials 4. Table 1 List of published clinical trials. Acute Phase of SCI Given that most of the animal preclinical experiments are conducted at the acute phase within 24 h of the injury [ 61 ], the lack of acute-phase clinical trials is somewhat surprising. Chronic Phase of SCI The majority of clinical trials are conducted in the chronic phase, when hope for a spontaneous recovery is minimal.
Hematopoietic Stem Cells Hematopoietic stem cells expressing CD34 and from both the bone marrow and peripheral blood are also relatively frequently used in clinical trials of SCI treatment [ 23 , 26 , 28 , 35 , 43 ]. OECs OECs surround olfactory neurons, with their presumed function as scavengers of pathogens and debris around the border between the central nervous system CNS and the nasal mucosa.
Schwann Cells Schwann cells act as structural scaffolds for the peripheral nervous system and can promote a microenvironment favorable to neuronal regeneration. NSCs NSCs are self-renewing, multipotent progenitor cells capable of differentiating into neural cells, oligodendrocytes, and astrocytes [ , ].
Cell Dose and Route Cell dose is among the most important clinical variables; however, it is difficult to determine the optimal dose in humans from the results of animal experiments because of the differences in body weight and spinal cord size. Table 2 Animal experiments comparing the efficacy of different cell administration routes. Patient Characteristics and Outcome Measures The ASIA impairment scale is the most frequently used metric for determining study inclusion, and often, only patients with the ASIA A impairment level complete motor and sensory loss below the level of injury are included in the trials.
Results, Pitfalls, and Future Directions Aside from the large number of experimental studies, clinical trials associated with SCI remains in its infancy.
Conclusions The heterogeneous results of clinical trials using stem cells for SCI treatment suggest a need for further assessment and basic experimentation. Author Contributions Conceptualization, M. Conflicts of Interest The authors declare no conflicts of interest. References 1. Jain N. Traumatic spinal cord injury in the United States, — Thompson C. The changing demographics of traumatic spinal cord injury: An year study of patients.
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Olfactory mucosal autografts and rehabilitation for chronic traumatic spinal cord injury. Dai G. Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury. Brain Res. Significant challenges remain for cell therapy trials in this area, including achieving stringent regulatory standards, ensuring appropriately powered efficacy trials, and establishing sustainable long-term funding.
However, cell therapies hold great promise for human spinal cord repair and future trials must continue to capitalize on the exciting developments emerging from preclinical studies. Keywords: Cell therapy; Regenerative medicine; Spinal cord injury; Spinal cord repair; Stem cells; Tissue engineering. Abstract Cell therapies have the potential to revolutionize the treatment of spinal cord injury.
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