A systematic review of large animal and human studies of stem cell therapeutics for acute adult traumatic spinal cord injury

Abstract Background: Traumatic spinal cord injury (TSCI) is a devastating condition and the search for a cure remains one of the most tenacious healthcare challenges to date. Current therapies are limited in their efficacy to restore full neurological function – resulting in lifelong disability and loss of autonomy. Whilst there remains a necessity to refine therapeutic protocols, stem cell (SC) studies have shown promise in the mending and re-establishment of the spinal cord neuroanatomy. Objectives: We conducted a systematic review of functional outcomes in stem cell therapeutics over the last three decades in large animals and humans. Methods: Medline, Embase, Cochrane and SCOPUS databases were searched for potentially pertinent articles from 1990 to 2020. Studies published in English were included if the stem cells were directly injected into the intraspinal, epidural or intrathecal compartments within two weeks of a traumatic mechanism of injury, including acute intervertebral disc prolapse. The participants were either large animals – defined as canine, porcine or non-human primate in-vivo models – or human patients. Results: Nine studies were included in this review. Statistically significant improvements in motor function and deep pain perception were seen at 8 weeks to 6 months post-SC injection compared to controls. Limitations: Functional outcomes are variably measured across studies. Almost all studies used experimentally induced trauma, which may not accurately represent the complexity of human spinal cord injury. Due to the exclusion criteria, there were no non-human primate studies included, yet these animal models are considered a closer anatomical match to humans than other large mammals. No human studies were included. Conclusions and Implications: Autologous and allogeneic stem cells have been trialled for the reconstitution of damaged and lost cells, remyelination of axons and remodelling of the pathophysiological microenvironment within the injured spinal cord, with some promising outcome data. This may translate to more successful future Phase I/II human clinical trials into the use of stem cells after TSCI in adults.