Efficacy and safety of stem cell therapy for acute and subacute ischemic stroke: a systematic review and meta-analysis

Abstract

The efficacy of stem cell therapy for ischemic stroke in terms of functional outcomes remains unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (PROSPERO: CRD42024503763) to assess the efficacy and safety of stem cell therapy for acute/subacute ischemic stroke, focusing on long-term outcomes. Studies of patients undergoing stem cell transplantation within 1 month of stroke onset were included. We searched five databases for publications up to January 17, 2024. Summary data were extracted from published reports. The primary outcome was the modified Rankin Scale (mRS) score. Measures of effect were risk ratios (RRs) with 95% confidence intervals (CIs). A random-effects model was used when I² was > 25%; otherwise, a fixed-effects model was used. Common serious adverse events were epilepsy, gastrointestinal disorders, and cardiac disorders. The risk of bias was assessed using the Cochrane Risk of Bias tool version 2. In total, 13 trials involving 872 (519 men) patients were included. The 1-year incidence of mRS scores 0-1 was higher in the cell-therapy group (45/195) than that in the control group (23/179; RR = 1.74 [95% CI = 1.09-2.77]; p = 0.020; I² = 0%). The 90-day incidence of mRS scores 0-2 was also higher (RR = 1.31 [95% CI = 1.01-1.70]; p = 0.044; I² = 0%). No significant differences were observed in serious adverse events or mortality. Stem cell therapy for acute/subacute ischemic stroke within 1 month of onset is safe and significantly improves long-term functional outcomes, although the mechanisms of action need to be elucidated and treatment protocols standardized to establish stem cell therapy as a standard care option for ischemic stroke.

Keywords: Assessment; Ischemic stroke; Outcome; Stem cell transplantation; Systematic review.

Fig. 1

PRISMA flow diagram.

Fig. 2

Forest plots comparing the risks of modified Rankin Scale (mRS) scores of 0–1 at 90, 180, and 365 days after treatment (a, b, and c), and the risks of mRS scores of 0–2 at 90, 180, and 365 days after treatment (d, e, and f).

Fig. 3

Forest plots comparing the mean differences in National Institutes of Health Stroke Scale scores at 90, 180, and 365 days after treatment (a, b, and c), the mean differences in Barthel Index scores at 90, 180, and 365 days after treatment (d, e, and f), the risks of serious adverse events up to the last follow-up (g), and the risks of mortality up to the last follow-up (h).

Fig. 4

Risk-of-bias summary for each included trial. Green represents a low risk of bias, yellow represents some concerns, and red represents a high risk of bias.