Exploration of Cytokines That Impact the Therapeutic Efficacy of Mesenchymal Stem Cells in Alzheimer’s Disease
Current therapies for Alzheimer’s disease (AD) includes acetylcholinesterase inhibitors, NMDA receptor antagonists, and amyloid beta (Aβ)/Tau-targeting drugs. While these drugs improve cognitive decline and target the pathological mechanisms, their outcomes still are still in debate. Mesenchymal ste...
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2025-06-01
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| author | Herui Wang Chonglin Zhong Yi Mi Guo Li Chenliang Zhang Yaoyao Chen Xin Li Yongjun Liu Guangyang Liu |
| author_facet | Herui Wang Chonglin Zhong Yi Mi Guo Li Chenliang Zhang Yaoyao Chen Xin Li Yongjun Liu Guangyang Liu |
| author_sort | Herui Wang |
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| description | Current therapies for Alzheimer’s disease (AD) includes acetylcholinesterase inhibitors, NMDA receptor antagonists, and amyloid beta (Aβ)/Tau-targeting drugs. While these drugs improve cognitive decline and target the pathological mechanisms, their outcomes still are still in debate. Mesenchymal stem cells (MSCs) offer a regenerative approach by modulating neuroinflammation and promoting neuroprotection. Although the paracrine of MSCs is efficient in various AD preclinical studies and the exosomes of MSCs have entered clinical trials, the key cytokines driving the efficacy remain unclear. Here, we evaluated human umbilical cord-derived MSCs (hUC-MSCs) and employed gene-silenced MSCs (siHGF-MSCs, siTNFR1-MSCs, siBDNF-MSCs) in APP/PS1 AD mice to investigate specific mechanisms. hUC-MSCs significantly reduced Aβ/Tau pathology and neuroinflammation, with cytokine-specific contributions: silencing HGF predominantly reduced Aβ/Tau clearance, although silencing TNFR1 or BDNF showed modest effects; silencing TNFR1 or BDNF more prominently weakened anti-neuroinflammation, while silencing HGF exerted a weaker influence. All three cytokines partially contributed to oxidative stress reduction and cognitive improvements. Our study highlights MSC-driven AD alleviation as a multifactorial strategy and reveals specific cytokines alleviating different aspects of AD pathology. |
| format | Article |
| id | doaj-art-9214ede11aee447caba59798f00e8bd2 |
| institution | Kabale University |
| issn | 2306-5354 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Bioengineering |
| spelling | doaj-art-9214ede11aee447caba59798f00e8bd22025-08-20T03:32:27ZengMDPI AGBioengineering2306-53542025-06-0112664610.3390/bioengineering12060646Exploration of Cytokines That Impact the Therapeutic Efficacy of Mesenchymal Stem Cells in Alzheimer’s DiseaseHerui Wang0Chonglin Zhong1Yi Mi2Guo Li3Chenliang Zhang4Yaoyao Chen5Xin Li6Yongjun Liu7Guangyang Liu8Stem Cell Biology and Regenerative Medicine Department, Yi-Chuang Institute of Bio-Industry, Beijing 100176, ChinaDepartment of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing 100053, ChinaStem Cell Biology and Regenerative Medicine Department, Yi-Chuang Institute of Bio-Industry, Beijing 100176, ChinaStem Cell Biology and Regenerative Medicine Department, Yi-Chuang Institute of Bio-Industry, Beijing 100176, ChinaStem Cell Biology and Regenerative Medicine Department, Yi-Chuang Institute of Bio-Industry, Beijing 100176, ChinaStem Cell Biology and Regenerative Medicine Department, Yi-Chuang Institute of Bio-Industry, Beijing 100176, ChinaStem Cell Biology and Regenerative Medicine Department, Yi-Chuang Institute of Bio-Industry, Beijing 100176, ChinaStem Cell Biology and Regenerative Medicine Department, Yi-Chuang Institute of Bio-Industry, Beijing 100176, ChinaStem Cell Biology and Regenerative Medicine Department, Yi-Chuang Institute of Bio-Industry, Beijing 100176, ChinaCurrent therapies for Alzheimer’s disease (AD) includes acetylcholinesterase inhibitors, NMDA receptor antagonists, and amyloid beta (Aβ)/Tau-targeting drugs. While these drugs improve cognitive decline and target the pathological mechanisms, their outcomes still are still in debate. Mesenchymal stem cells (MSCs) offer a regenerative approach by modulating neuroinflammation and promoting neuroprotection. Although the paracrine of MSCs is efficient in various AD preclinical studies and the exosomes of MSCs have entered clinical trials, the key cytokines driving the efficacy remain unclear. Here, we evaluated human umbilical cord-derived MSCs (hUC-MSCs) and employed gene-silenced MSCs (siHGF-MSCs, siTNFR1-MSCs, siBDNF-MSCs) in APP/PS1 AD mice to investigate specific mechanisms. hUC-MSCs significantly reduced Aβ/Tau pathology and neuroinflammation, with cytokine-specific contributions: silencing HGF predominantly reduced Aβ/Tau clearance, although silencing TNFR1 or BDNF showed modest effects; silencing TNFR1 or BDNF more prominently weakened anti-neuroinflammation, while silencing HGF exerted a weaker influence. All three cytokines partially contributed to oxidative stress reduction and cognitive improvements. Our study highlights MSC-driven AD alleviation as a multifactorial strategy and reveals specific cytokines alleviating different aspects of AD pathology.https://www.mdpi.com/2306-5354/12/6/646Alzheimer’s diseaseneuroinflammationcognitionnerve regenerationmesenchymal stem cells |
| spellingShingle | Herui Wang Chonglin Zhong Yi Mi Guo Li Chenliang Zhang Yaoyao Chen Xin Li Yongjun Liu Guangyang Liu Exploration of Cytokines That Impact the Therapeutic Efficacy of Mesenchymal Stem Cells in Alzheimer’s Disease Bioengineering Alzheimer’s disease neuroinflammation cognition nerve regeneration mesenchymal stem cells |
| title | Exploration of Cytokines That Impact the Therapeutic Efficacy of Mesenchymal Stem Cells in Alzheimer’s Disease |
| title_full | Exploration of Cytokines That Impact the Therapeutic Efficacy of Mesenchymal Stem Cells in Alzheimer’s Disease |
| title_fullStr | Exploration of Cytokines That Impact the Therapeutic Efficacy of Mesenchymal Stem Cells in Alzheimer’s Disease |
| title_full_unstemmed | Exploration of Cytokines That Impact the Therapeutic Efficacy of Mesenchymal Stem Cells in Alzheimer’s Disease |
| title_short | Exploration of Cytokines That Impact the Therapeutic Efficacy of Mesenchymal Stem Cells in Alzheimer’s Disease |
| title_sort | exploration of cytokines that impact the therapeutic efficacy of mesenchymal stem cells in alzheimer s disease |
| topic | Alzheimer’s disease neuroinflammation cognition nerve regeneration mesenchymal stem cells |
| url | https://www.mdpi.com/2306-5354/12/6/646 |
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