Mesenchymal Stem Cell Therapy for Traumatic Spinal Cord Injury -Is the Hype Worth the Hope?

Introduction: Several preclinical studies and clinical trials have revealed that stem cells can be used to repair spinal cord injury (SCI) because of their self-renewal property and capacity for neuronal-like differentiation into a functional neural cell to form new synapses, release various neurotrophic factors, and provide an appropriate conducive microenvironment to promote neuronal repair. Although the reliability of such treatment methodology for SCI is being tested in human subjects by a few clinical trials, they provide us with conflicting results and thereby clouding the only ray of hope for SCI patients. Hence, we aim to analyze the evidence in literature on efficacy and safety of Mesenchymal Stem Cell(MSC) therapy in human subjects with traumatic Spinal Cord Injury(SCI) and identify its potential role in the management of SCI. Materials and Methods: We conducted independent and duplicate electronic database searches including PubMed, Embase and Cochrane Library till May 2020 for studies analyzing efficacy and safety of stem cell therapy for SCI. AIS grade improvement, ASIA sensorimotor score, activities of daily living score, residual urine volume, bladder function improvement, SSEP improvement and adverse reactions were the outcomes analyzed. Analysis was performed in R-platform using OpenMetaAnalyst software. Results: 19 studies involving 670 patients were included for analysis. On analysis intervention group showed statistically significant improvement in AIS grade (P {\textless} .001), ASIA sensory score (P {\textless} .017) along with light-touch (P {\textless} .001) and pinprick (P = .046), bladder function (P = .012), residual urine volume reduction (P = .023) and SSEP improvement (P = .002) respectively. However, no significant difference was noted in motor score (P = .193) and activities of daily living score (P = .161). Although intervention group had significant increase in complications (P {\textless} .001), no serious or permanent adverse events were reported. On subgroup analysis, low concentration of MSC ({\textless}5 x 107 cells) and initial AIS grade-A presentation showed significantly better outcomes than their counterparts. Conclusion: Our analysis establishes the efficacy and safety of MSC transplantation in terms of improvement in AIS grade, ASIA sensory scores, bladder function and electrophysiological parameters like SSEP compared to controls, without major adverse events. However, further research is needed to standardize dose, timing, route and source of MSCs used for transplantation.