Embryonic stem cell-derived neural stem cell transplantation in experimental ischemic stroke: A systematic review and meta-analysis
TL;DR
ESC-NSC transplantation may enhance locomotor and neurological recovery and reduce tissue damage in experimental ischemic stroke, particularly when administered in the early post-ischemic phase, due to methodological heterogeneity, small sample sizes, and low-to-moderate certainty of evidence.
Abstract
Background: Stem cell therapy holds promise for neural repair after ischemic injury. This systematic review and meta-analysis evaluated the efficacy of embryonic stem cell-derived neural stem/progenitor cells (ESC-NSCs) in experimental ischemic stroke. Methods: Preclinical animal studies were identified through MEDLINE, Embase, Scopus, and Web of Science by February 2024. Screening, data extraction, and risk-of-bias assessment (SYRCLE tool) were performed independently by two reviewers. Results: Twenty-three studies met inclusion criteria. Pooled analyses indicated that ESC-NSC transplantation improved locomotion [standardized mean difference (SMD) = 0.57; 95% confidence interval (CI): 0.34 to 0.80; P < 0.001] and neurological status assessed by the cylinder test (SMD = 0.69; 95% CI: 0.29 to 1.08; P = 0.001), while reducing infarct volume (SMD = -0.26; 95% CI: -0.50 to -0.02; P = 0.030) and astrocytosis [glial fibrillary acidic protein (GFAP)⁺ cells; SMD = -3.02; 95% CI: -3.87 to -2.18; P < 0.001]. No significant effect was observed on inflammation [ionizing calcium-binding adaptor molecule 1 (Iba-1)⁺ cells; SMD = -3.69; 95% CI: -10.03 to 2.64; P = 0.254]. Subgroup analyses showed greater locomotor improvement when ESC-NSCs were administered 24-72 hours after stroke, in both neonatal and adult models. Most included studies had an unclear risk of bias in randomization and blinding domains. According to Grading of Recommendations Assessment, Development, and Evaluation (GRADE), the certainty of evidence was low to moderate for the main outcomes. Conclusion: ESC-NSC transplantation may enhance locomotor and neurological recovery and reduce tissue damage in experimental ischemic stroke, particularly when administered in the early post-ischemic phase. However, due to methodological heterogeneity, small sample sizes, and low-to-moderate certainty of evidence, these findings should be interpreted with caution.