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Meta-Analysis
. 2020 May 27;9(1):20.
doi: 10.1186/s40035-020-00199-x.

Transplantation of bone marrow mesenchymal stem cells improves cognitive deficits and alleviates neuropathology in animal models of Alzheimer's disease: a meta-analytic review on potential mechanisms

Chuan Qin  1 , Yalan Lu  2 , Kewei Wang  2 , Lin Bai  2 , Guiying Shi  2 , Yiying Huang  2 , Yongning Li  3
Affiliations
Meta-Analysis

Transplantation of bone marrow mesenchymal stem cells improves cognitive deficits and alleviates neuropathology in animal models of Alzheimer's disease: a meta-analytic review on potential mechanisms

Chuan Qin et al. Transl Neurodegener. .

Abstract

Background: Alzheimer's disease is a neurodegenerative disorder. Therapeutically, a transplantation of bone marrow mesenchymal stem cells (BMMSCs) can play a beneficial role in animal models of Alzheimer's disease. However, the relevant mechanism remains to be fully elucidated.

Main body: Subsequent to the transplantation of BMMSCs, memory loss and cognitive impairment were significantly improved in animal models with Alzheimer's disease (AD). Potential mechanisms involved neurogenesis, apoptosis, angiogenesis, inflammation, immunomodulation, etc. The above mechanisms might play different roles at certain stages. It was revealed that the transplantation of BMMSCs could alter some gene levels. Moreover, the differential expression of representative genes was responsible for neuropathological phenotypes in Alzheimer's disease, which could be used to construct gene-specific patterns.

Conclusions: Multiple signal pathways involve therapeutic mechanisms by which the transplantation of BMMSCs improves cognitive and behavioral deficits in AD models. Gene expression profile can be utilized to establish statistical regression model for the evaluation of therapeutic effect. The transplantation of autologous BMMSCs maybe a prospective therapy for patients with Alzheimer's disease.

Keywords: Alzheimer’s disease; Amyloid β peptide; Animal model; Bone marrow mesenchymal stem cells; Cognitive deficits; Memory loss; Meta-analysis; Neuropathology.

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Conflict of interest statement

The authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
Transplantation of bone marrow mesenchymal stem cells could improve clinical manifestations in animal models with Alzheimer’s disease. Flow chart summarized relevant references that was identified and included in the meta-analytic review
Fig. 2
Fig. 2
Summary of potential bias in the identified studies
Fig. 3
Fig. 3
Transplantation of bone marrow mesenchymal stem cells could improve behavioral deficits in animal models of Alzheimer’s disease, which was generally characterized by abnormal manifestation or relationship. The beneficial change might be a temporary or permanent effect when compared to previous behavior. a. Behavioral changes as demonstrated through Y-maze test; b. Behavioral changes by Morris water maze test
Fig. 4
Fig. 4
Meta-analysis on potential mechanisms. The transplantation of BMMSCs could alleviate neuropathology through diverse mechanisms, such as to decrease the number of hippocampal Aβ plaques as demonstrated in AD animal models (a). The Fig. 4a was plotted by relative ratio. The value in experimental group was assigned as 1 and the same as the following figures; to stimulate neurogenesis, neuronal differentiation, and neuronal integration (b); to promote angiogenesis in brain tissue as reflected by VEGF marker (c, d); to attenuate Aβ-induced apoptotic cell death in both primary hippocampal neurons and Aβ-injected animal models (e, f); immunomodulation and neuroprotection (g); to inhibit neuroinflammation in AD animal models (h)
Fig. 5
Fig. 5
Construction of gene-specific regression model. a. Differential gene expression was compared between control and samples of patients with Alzheimer’s disease. b. Hierarchical cluster analysis based on the comparison between control and gene data from samples of patients with Alzheimer’s disease. c. Heatmap of gene data from brain samples of patients with Alzheimer’s disease. d. Sigmoid curve of gene pattern. e. Logistic regression equation for prediction of gene-specific patterns of Alzheimer’s disease
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