About 273,000 people with traumatic spinal cord injuries live in the U.S. today. SCI imposes enormous financial, emotional and psychological burdens on the patients, their families and the society in which they live.
Partial or total loss of neural functions is normally the result of direct mechanical damage to the spinal cord. The most frequent causes for SCI in 2010 were motor vehicle accidents (36.5 percent), falls (28.5 percent) and acts of violence (14.3 percent).
The average age of injury has been calculated to be 42.6 years with 81 percent of them occurring in males. Unfortunately, only 1 percent of SCI patients experience complete neurologic recovery by the time of hospital discharge.
Despite years of research, treatments for paralysis are limited to steroid administration in high doses, acute surgical intervention to stabilize and decompress the spinal cord or rehabilitative care. Therefore, SCI remains a harmful disease without any definitive cure.
Over the course of the past decade, tremendous progress has been observed in our level of understanding of events caused by SCI at the molecular and cellular level, leading to insights into mechanisms of tissue damage and failure of injured neuronal regeneration.
Several research centers and scientific groups have tried different cell-mediated regenerative therapies following human spinal cord injury with positive results by trying different types of cells. Furthermore, a large number of clinical studies are ongoing with cell-mediated regenerative therapeutics and neuronal stem cells.
The results of these studies have suggested that the current transplantation therapeutics could be relatively safe with variable levels of neurological recovery.
Different factors could theoretically hinder the introduction of a specific clinical therapy in this field, including:
- type of complication
- type of causes for the injury
- target population selection criteria
- transplantation material optimization
- different levels of patient recovery potential
- lack of quantitative and sensitive methods to assess injury and recovery
- the need for a combination for a majority of cases
Therefore, a good clinical trial design in this field would require a large sample size to address all of these factors and to minimize type II errors. Furthermore, there is a need for highly sensitive techniques for the evaluation of the changes in motor, sensory, autonomic and other functions.
On the other hand, the ability to pursue a multimodality approach of that nature would require a high degree of collaboration between multiple entities involved, including: clinical centers, research institutes, government research support bodies. Last but not least, there should be a vast amount of budgeterial support behind a good clinical trial that can provide meaningful and reliable results in this field.
The other side of the game is that there are several gray areas in cell-based and stem cell-based therapies, requiring further research to improve the effectiveness of the cell-based therapies in SCI. Seven specific gray areas have been highlighted in the literature, including:
- the gap between animal model and human subjects
- uncertainty regarding the time, route and the dosage of cell application
- cell source
- lack of solution for SCI vascular composition
- absence of a visible tracking methodology for transplanted cells
- scaffold-mediated housing of cells at the site of injury
- specific physical and chemical stimuli that is required for the formulation of functional synaptic formation
In summary, cell- and gene-based therapies, bone marrow-derived mesenchymal stem cells (BMSC), adipose tissue-derived mesenchymal stem cells, human umbilical cord blood-derived MSCs and human WHARTON's jelly/umbilical cord matrix cells are the subjects of active research to help in SCI treatment.
Novel therapeutic approaches using MSCs hold great promise for the treatment of spinal cord injury, but cell-based therapy is still in its early stages with several gray areas and challenges to be addressed. Therefore, there is a need for continued research to unravel mechanism of action of MSCs transplantation by conducting large-scale multicenter, controlled randomized trials.
