The functional mechanism of bone marrow-derived mesenchymal stem cells in the treatment of animal models with Alzheimer's disease: crosstalk between autophagy and apoptosis

Chuan Qin; Lin Bai; Yongning Li; Kewei Wang

doi:10.1186/s13287-022-02765-8

The functional mechanism of bone marrow-derived mesenchymal stem cells in the treatment of animal models with Alzheimer's disease: crosstalk between autophagy and apoptosis

Stem Cell Res Ther. 2022 Mar 3;13(1):90. doi: 10.1186/s13287-022-02765-8.

Authors

Chuan Qin¹, Lin Bai¹, Yongning Li², Kewei Wang³

Affiliations

¹ Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Comparative Medical Center, Peking Union Medical College, 5 Panjiayuan Nanli St., Beijing, 100021, China.
² Department of International Medical Service and Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan 1, Dong Cheng District, Beijing, 100730, China.
³ Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Comparative Medical Center, Peking Union Medical College, 5 Panjiayuan Nanli St., Beijing, 100021, China. kkww02052015@hotmail.com.

Abstract

The transplantation of bone marrow-derived mesenchymal stem cells (BMMSCs) alleviates neuropathology and improves cognitive deficits in animal models with Alzheimer's disease. However, the underlying mechanism remains undefined. Based on meta-analysis and comprehensive review, high-profile studies support the theory that transplanted BMMSCs activate autophagy, as evidenced by the expression levels of signal molecules such as Beclin-1, Atg5, LC3-II, and mTOR. Functional autophagy mitigates neuronal apoptosis, which is reflected by the alterations of IAPs, Bcl-2, caspase-3, and so forth. Moreover, the transplantation of BMMSCs can decrease aberrant amyloid-beta peptides as well as tau aggregates, inhibit neuroinflammation, and stimulate synaptogenesis. There is a signal crosstalk between autophagy and apoptosis, which may be regulated to produce synergistic effect on the preconditioning of stem cells. Forasmuch, the therapeutic effect of transplanted BMMSCs can be enhanced by autophagy and/or apoptosis modulators.

Keywords: Alzheimer’s disease; Apoptosis; Autophagy; Bone marrow-derived mesenchymal stem cells.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Alzheimer Disease* / therapy
Animals
Apoptosis / physiology
Autophagy / physiology
Bone Marrow
Disease Models, Animal
Mesenchymal Stem Cells* / metabolism
Models, Animal