Stem cells from human exfoliated deciduous teeth affect mitochondria and reverse cognitive decline in a senescence-accelerated mouse prone 8 model
| Autor: | Xiaoshuang Zhang, Jinghui Zhang, Cencan Xing, Zehua Zeng, Wenhuan Guo, Roshan Shah, Yongzhong Bian, Jingjie Yang, Wangyu Bi, Donghui Wang, Yingxian Li, Hongwu Du |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Senescence
Aging Cancer Research medicine.medical_treatment Immunology Mitochondrion Biology Mice Alzheimer Disease In vivo medicine Animals Humans Immunology and Allergy Cognitive Dysfunction Tooth Deciduous Cognitive decline Maze Learning Genetics (clinical) Transplantation Stem Cells Cell Biology Stem-cell therapy medicine.disease Mitochondria Barnes maze Cell biology Disease Models Animal Oncology Alzheimer's disease Stem cell |
| Zdroj: | Cytotherapy. 24:59-71 |
| ISSN: | 1465-3249 |
| DOI: | 10.1016/j.jcyt.2021.07.018 |
| Popis: | Background aims Stem cell therapy is a novel therapy being explored for AD. The molecular mechanism of its effect is still unclear. The authors investigated the effects and mechanism by injection of SHEDs into an AD mouse model. Methods SHEDs were cultured in vitro and injected into AD SAMP8 mice by caudal vein, and SHEDs labeled via synthetic dye showed in vivo migration to the head. The cognitive ability of SAMP8 mice was evaluated via Barnes maze and new object recognition. The pathological indicators of AD, including Tau, amyloid plaques and inflammatory factors, were examined at the protein or RNA level. Next, macro-proteomics analysis and weighted gene co-expression network analysis (WGCNA) based on protein groups and behavioral data were applied to discover the important gene cluster involved in the improvement of AD by SHEDs, which was further confirmed in an AD model in both mouse and cell lines. Results SHED treatment improved the cognitive ability and pathological symptoms of SAMP8 mice. Proteomics analysis indicated that these improvements were tightly related to the mitochondria, which was proved through examination of the shape and function of mitochondria both in vivo (SAMP8 brain) and in vitro (SH-SY5Y cells). Finally, the core targets of SHEDs in the mitochondrial pathway, Hook3, Mic13 and MIF, were screened out and confirmed in vivo. Conclusions SHED treatment significantly relieved AD symptoms, improved cognitive ability and reversed memory loss in an AD mouse model, possibly through the recovery of dysfunctional mitochondria. These results raise the possibility that SHED may ease the symptoms of AD by targeting the mitochondria. |
| Databáze: | OpenAIRE |
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