Chinese Journal of Tissue Engineering Research ›› 2022, Vol. 26 ›› Issue (19): 2964-2969.doi: 10.12307/2022.372

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Mechanism by which bone marrow mesenchymal stem cells improve cognitive function in APP/PS1 double transgenic mice

Gu Qingfang1, Guo Minfang1, Liu Xiaoqin1, Mu Bingtao1, Li Weimei1, Song Lijuan2, Chai Zhi2, Ma Cungen1, 2, Yu Jiezhong1   

  1. 1Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, Datong 037009, Shanxi Province, China; 2Research Center of Neurobiology, Key Laboratory of Multiple Sclerosis, Nourishing Qi and Activating Blood of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Taiyuan 030629, Shanxi Province, China
  • Received:2021-01-07 Revised:2021-02-10 Accepted:2021-07-22 Online:2022-07-08 Published:2021-12-28
  • Contact: Yu Jiezhong, MD, Professor, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, Datong 037009, Shanxi Province, China Ma Cungen, MD, Professor, Doctoral supervisor, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, Datong 037009, Shanxi Province, China; Research Center of Neurobiology, Key Laboratory of Multiple Sclerosis, Nourishing Qi and Activating Blood of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Taiyuan 030629, Shanxi Province, China
  • About author:Gu Qingfang, Master, Lecturer, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, Datong 037009, Shanxi Province, China
  • Supported by:
    the Open Project of the Key Laboratory of Medical Resources and Natural Medicine Chemistry of the Ministry of Education, No. 2019004 (to MCG); the Neurodegenerative Disease Project of Key Laboratory of Shanxi Province, No. 201805D111009 (to MCG), No. 201805D131005 (to YJZ); the Basic Research Program of Datong Science and Technology Bureau, Shanxi Province, No. 2017136 (to GQF); the Applied Basic Research Project of Shanxi Province, No. 201901D111334 (to SLJ), No. 2018TD-012 (to CZ); the Open Project of the State Key Laboratory of Molecular Developmental Biology, Chinese Academy of Sciences, No. 2020-MDB-KF-09 (to SLJ)

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Abstract: BACKGROUND: Studies have shown that bone marrow mesenchymal stem cell therapy can effectively fill the neurons lost in Alzheimer’s disease patients, but the specific mechanism of action needs to be further clarified.  
OBJECTIVE: To explore the therapeutic effects of bone marrow mesenchymal stem cells in APP/PS1 double transgenic mice with Alzheimer’s disease and its mechanism.
METHODS:  APP/PS1 double transgenic mice were selected as the research objects and were randomly divided into model and bone marrow mesenchymal stem cell groups (n=10 per group). Ten wild-type C57BL/6 mice of the same month and the same sex were selected as the normal control group. The mice were treated with bone marrow mesenchymal stem cells (1×106/time) or normal saline, and repeated administration once a week, for 2 months via nasal cavity. Morris water maze test was applied to examine cognitive function of mice. Western blot assay was used to detect the expression of related factors of pathological markers, inflammatory molecules and oxidative stress proteins in the brain tissues of mice.  
RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cells effectively improved the cognitive dysfunction of Alzheimer’s disease mice, increased the expression of APP protein and decreased expression of phosphorylated tau protein, reduced the expression of Toll like receptor 2, inducible nitric oxide synthase, nuclear transcription factor kappa B and increased the expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1. It is concluded that bone marrow mesenchymal stem cells have a potential role in the treatment of Alzheimer’s disease; the mechanism exerts the effects of the anti-inflammation and antioxidation through nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway.

Key words: stem cells, bone marrow mesenchymal stem cells, Alzheimer’s disease, oxidative stress, nuclear factor E2 related factor 2, heme oxygenase 1, signaling pathway

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