Stem Cell Therapy for Spinal Cord Injury

Abstract

Traumatic spinal cord injury (SCI) results in direct and indirect damage to neural tissues, which results in motor and sensory dysfunction, dystonia, and pathological reflex that ultimately lead to paraplegia or tetraplegia. A loss of cells, axon regeneration failure, and time-sensitive pathophysiology make tissue repair difficult. Despite various medical developments, there are currently no effective regenerative treatments. Stem cell therapy is a promising treatment for SCI due to its multiple targets and reactivity benefits. The present review focuses on SCI stem cell therapy, including bone marrow mesenchymal stem cells, umbilical mesenchymal stem cells, adipose-derived mesenchymal stem cells, neural stem cells, neural progenitor cells, embryonic stem cells, induced pluripotent stem cells, and extracellular vesicles. Each cell type targets certain features of SCI pathology and shows therapeutic effects via cell replacement, nutritional support, scaffolds, and immunomodulation mechanisms. However, many preclinical studies and a growing number of clinical trials found that single-cell treatments had only limited benefits for SCI. SCI damage is multifaceted, and there is a growing consensus that a combined treatment is needed.

Elucidating the Pivotal Neuroimmunomodulation of Stem Cells in Spinal Cord Injury Repair

“…Furthermore, the cells were never detected in analogous areas of the spinal cord of noninjured animals. These findings were coherent with the postulation that UCBCs migrate to and partake in the healing of neurological defects after SCI [ 170 , 171 ]. Studies further demonstrated that transplanted human UCBCs differentiated into several neural cells, stimulated renewal of spinal cord tissue, and enhanced motor function in SCI rat models [ 172 – 175 ].…”

“…UCBCs have a high rate of hematopoietic stem and progenitor cells; they are native of the immune cells and also possess nonhematopoietic cells that have therapeutic potentials [ 169 ]. Initial study demonstrated that human cord blood leukocytes were advantageous in reversing the behavioral effects of SCI, even when transplanted five days after injury [ 170 , 171 ].…”

“…Also, human UCBCs transplanted into injured rat spinal cord models revealed that the UCBCs appeared in injured areas, but not in noninjured areas of rat spinal cords [ 170 , 171 ]. Furthermore, the cells were never detected in analogous areas of the spinal cord of noninjured animals.…”

Future Perspectives in Spinal Cord Repair: Brain as Saviour? TSCI with Concurrent TBI: Pathophysiological Interaction and Impact on MSC Treatment

“…Stem cells are multipotent cells with the ability to differentiate into various cell types, as well as, to renew themselves [ 236 ]. Mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), brain-derived neural stem cells (NSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), which are reprogrammed from somatic cells, represent major stem cell sources previously investigated for traumatic brain injury, spinal cord injury, neurodegenerative disease and stroke therapy [ 84 , 237 , 238 , 239 , 240 , 241 , 242 , 243 , 244 , 245 , 246 , 247 , 248 , 249 ] ( Table 1 ).…”

“…There are currently several trials in progress and their completion will deliver the required data on the efficacy of MSC therapies after TSCI [ 84 , 274 ]. For a brief summary of stem-cell based therapies in TSCI, we refer to Table 1 and other recent reviews [ 19 , 246 , 272 , 275 ]. Overall, MSC therapy improves the microenvironment of the injury site, improves nutritional support, modulates the inflammatory response, and reduces blood–brain and blood–spinal cord barrier leakage, all of which help with TSCI healing [ 274 ].…”