Effects of mesenchymal stem cells transplantation on cognitive deficits in animal models of Alzheimer's disease: A systematic review and meta-analysis.

Yunli Zhao,Yunxia Zhang,Birong Dong,Qiukui Hao,Meiling Ge

doi:10.1002/brb3.982

Abstract

BackgroundAlzheimer’s disease (AD) is a globally prevalent neurodegenerative disease, clinically characterized by progressive memory loss and gradual impairment of cognitive functions. Mesenchymal stem cells (MSCs) transplantation has been considered a possible therapeutic method for Alzheimer’s disease (AD). However, no quantitative data synthesis of MSC therapy for AD exists. We conducted a systematic review and meta‐analysis to study the effects of MSCs on cognitive deficits in animal models of AD.MethodsWe identified eligible studies published from January 1980 to January 2017 by searching four electronic databases (PubMed, MEDLINE, EMBASE, CNKI). The endpoint was the effects of MSCs on cognitive performance evaluated by the Morris water maze (MWM) test including escape latency, and/or number of platform crossing, and/or time in the target quadrant.ResultsNine preclinical studies incorporating 225 animals with AD were included for the meta‐analysis. The studies indicated that MSC‐based treatment significantly improved the learning function through measurements of the escape latency (SMD = −0.99, 95% CI = −1.33 to −0.64, p < .00001). Additionally, we observed that transplantation of MSCs significantly increased the number of platform crossing in six experiments (SMD = 0.78, 95% CI = 0.43 to 1.13, p < .0001). What’s more, the times in the target quadrant were increased in five studies indicated that transplantation of MSCs could ameliorate the cognitive impairments (SMD = 1.06, 95% CI = 0.46 to 1.67, p = .0005).ConclusionsThis study showed that MSC transplantation could reduce cognitive deficits in AD models. These findings support the further studies to translate MSCs in the treatment of AD in humans

Highlights

Alzheimer’s disease (AD), the leading cause of dementia, is an age- related neurodegenerative disease
We observed that transplantation of Mesenchymal stem cells (MSCs) significantly increased the number of platform crossing in six experiments (SMD = 0.78, 95% CI = 0.43 to 1.13, p < .0001)
What’s more, five studies reported the impact of MSC transplantation on increasing time in target quadrant compared with the control group. (Banik et al, 2015; Kim et al, 2013; Peng et al, 2014; Yang, Yang, et al, 2013), and the data indicated significant effectiveness of MSCs compared with the control group (SMD = 1.06, 95% CI = 0.46 to 1.67, p = .0005. heterogeneity, I2 = 61%, p = .04) (Figure 2c)

Summary

| INTRODUCTION

Alzheimer’s disease (AD), the leading cause of dementia, is an age- related neurodegenerative disease. Different cell replacement therapies have been tested in both animal models and clinical trials and become a promising approach to treat comprehensive human diseases, such as ischemic heart disease, autoimmune diseases, and neurological disorders (Bel et al, 2003; Gratwohl et al, 2010; Kaigler et al, 2013). A number of reports on stem cell transplantation in AD animal models indicate improvement in cognitive and memory performances and increased neuronal survival. Therapeutic effects of transplantation of MSCs into a murine model of AD have been reported. We will assess the effect of MSC transplantation on cognitive performance by evaluating the performance of various mouse strains in the Morris water maze (MWM) test. The MWM test is a well-established tool for measuring spatial learning and memory in mouse, and widely used in AD research (Vorhees & Williams, 2006)

| MATERIALS AND METHODS

Escape latency

Quality abc d

| DISCUSSION

Findings

| CONCLUSIONS