STEM CELL THERAPY IN PATIENTS WITH ISCHEMIC STROKE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Background and Objective: Stem cell therapy has emerged as a potential therapy for the treatment of stroke. We performed a systematic review and meta-analysis of published randomized controlled studies using various types of stem cell therapies in patients with ischemic stroke (IS). Method: Literature search was carried out using PubMed, Google Scholar, Cochrane library, and clinicaltrial.gov to identify studies on stem cell therapy in IS from its inception till January 2020. Data were extracted independently by two reviewers. STATA version 13 was used for carrying out meta- analysis. We included only randomized controlled trials (RCTs) if any of the stem cell therapy was used to treat patients with IS in any phase after the index stroke. Results: We included a total of eight randomized controlled studies involving 459 subjects (217 intervention and 242 controls) in the meta-analysis. We did not observe statistically significant reduction in mean NIHSS score in the intervention group (SMD - 0.34, 95% CI - 0.76 to 0.08) in patients with acute or sub-acute stroke. However, a statistically significant reduction (SMD - 1.57, 95% CI -2.22 to -0.92) was observed in patients with chronic ischemic stroke. Statistically non-significant reduction in mean mRS in the intervention group (SMD 0.04, 95% CI -0.20 to 0.28) in patients with acute or sub-acute ischemic stroke was observed, however a statistically significant reduction (SMD - 1.07, 95% CI - 1.94 to -0.19) was noted in patients with chronic stroke. We did not observe statistically significant reduction in mean Barthel index score (SMD 0.24, 95%CI -1.69 to 2.17) in chronic stroke. Statistically non-significant lower mortality rate was observed in intervention group compared to controls (Risk Ratio 0.84, 95% CI 0.43 to 1.66) among acute or sub-acute, as well as in the chronic stroke group (Risk Ratio 0.47, 95% CI 0.20 to 1.09). Conclusion: Our meta-analysis provides no clinically important evidence for efficacy of stem cells in reducing neurological deficit compared to control group. Well-designed large randomized controlled trials are required to provide more information on the efficacy of stem cell therapy in patients with IS.