Neural stem/progenitor cell therapy for Alzheimer disease in preclinical rodent models: a systematic review and meta-analysis.

Background: Alzheimer's disease (AD) is a common progressive neurodegenerative disease characterized by memory impairments, and there is no effective therapy. Neural stem/progenitor cell (NSPC) has emerged as potential novel therapy for AD, and we aim to explore whether neural stem/progenitor cell therapy was effective for rodent models of AD.

Methods: We searched PubMed, Embase, Cochrane Library and Web of Science up to December 6, 2022. The outcomes included cognitive function, pathological features and BDNF. The GetData Graph Digitizer software (version 2.26) was applied to extract numerical values, and RevMan 5.3 and Stata 16 were used to analyze data. The SYRCLE risk of bias tool was used to assess study quality.

Results: We evaluated 22 mice studies and 8 rat studies. Compared to control groups, cognitive function of NSPC groups of both mice studies (SMD =  - 1.96, 95% CI  - 2.47 to  - 1.45, I = 75%, P < 0.00001) and rat studies (SMD =  - 1.35, 95% CI - 2.11 to  - 0.59, I = 77%, P = 0.0005) was apparently improved. In mice studies, NSPC group has lower Aβ deposition (SMD =  - 0.96, 95% CI  - 1.40 to  - 0.52, P < 0.0001) and p-tau level (SMD =  - 4.94, 95% CI  - 7.29 to  - 2.95, P < 0.0001), higher synaptic density (SMD = 2.02, 95% CI 0.50-3.55, P = 0.009) and BDNF (SMD = 1.69, 95% CI 0.61-2.77, P = 0.002). Combined with nanoformulation (SMD =  - 1.29, 95% CI  - 2.26 to  - 0.32, I = 65%, P = 0.009) and genetically modified (SMD =  - 1.29, 95% CI  - 1.92 to  - 0.66, I = 60%, P < 0.0001) could improve the effect of NSPC. In addition, both xenogeneic and allogeneic transplant of NSPC could reverse the cognitive impairment of AD animal models.

Conclusions: Our results suggested that NSPC therapy could improve the cognitive function and slow down the progression of AD. Due to the limitations of models, more animal trials and clinical trials are needed.