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Transplantation of Nasal Olfactory Mucosa Mesenchymal Stem Cells Benefits Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is a common neurodegenerative disease that contributes to 60–70% of dementia in elderly people and is currently incurable. Current treatments only relieve the symptoms of AD and slow its progression. Achieving effective neural regeneration to ameliorate cognitive impairment is a major challenge in the treatment of AD. For the first time, we alleviated symptoms of AD in APPswe/PS1dE9 mice (hereafter referred to as AD mice) by transplantation of olfactory mucosa mesenchymal stem cells (OM-MSCs). Our study demonstrated that OM-MSC transplantation promotes amyloid-β (Aβ) clearance, downregulates the inflammatory response, and increases the M2/M1 ratio; OM-MSCs promote the conversion of BV2 (microglia) from M1 to M2 and also Aβ clearance in SH-SY5YAPPswe (AD cell model). OM-MSC-transplanted AD mice show improved cognitive learning and locomotive behavior. Our study suggests that OM-MSC transplantation could alleviate the symptoms of AD and promote Aβ clearance through immunomodulation, thus demonstrating the great potential and social value of OM-MSC treatment for AD patients.

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All data are available from the corresponding author upon reasonable request.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (Grant Nos. 82172502 and 81974127) and Fundamental Research Funds for the Central Universities of Central South University (2019zzts1042, 2020zzts859).

Author information

Author notes

  1. Chun-Gu Hong, Meng-Lu Chen, Ran Duan, Ming Lu, Hui Xie, and Zheng-Zhao Liu contributed equally.

Authors and Affiliations

  1. Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Chun-Gu Hong, Hui Xie & Zheng-Zhao Liu

  2. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Chun-Gu Hong, Hui Xie & Zheng-Zhao Liu

  3. Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Meng-Lu Chen, Ran Duan, Xin Wang, Zhi-Lin Pang, Hui Xie & Zheng-Zhao Liu

  4. Department of Neurosurgery, Second Affiliated Hospital of Hunan Normal University (921 Hospital of PLA), Changsha, 410081, Hunan, China

    Li-Te Ge & Ming Lu

  5. Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China

    Li-Te Ge

Authors
  1. Chun-Gu Hong
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Contributions

Z.Z.L. conceived the study, designed the experimental procedures, analyzed the data, prepared the manuscript, and supervised the project. M.L.C. and C.G.H. performed the experiments and analyzed the data. X.W. and Z.L.P. performed the experiments. R.D. prepared the manuscript. M.L. and L.T.G. conceived the study. H.X. provided the platform for animal experiments and supervised the project.

Corresponding authors

Correspondence to Ming Lu, Hui Xie or Zheng-Zhao Liu.

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This study was approved by the Ethical Review Board at Xiangya Hospital of Central South University, Changsha, China (No. 2022010004).

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Hong, CG., Chen, ML., Duan, R. et al. Transplantation of Nasal Olfactory Mucosa Mesenchymal Stem Cells Benefits Alzheimer’s Disease. Mol Neurobiol 59, 7323–7336 (2022). https://doi.org/10.1007/s12035-022-03044-6

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