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Distinct Effects of the Hippocampal Transplantation of Neural and Mesenchymal Stem Cells in a Transgenic Model of Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is a severe disabling condition with no cure currently available, which accounts for 60–70% of all dementia cases worldwide. Therefore, the investigation of possible therapeutic strategies for AD is necessary. To this end, animal models corresponding to the main aspects of AD in humans have been widely used. Similar to AD patients, the double transgenic APPswe/PS1dE9 (APP/PS1) mice show cognitive deficits, hyperlocomotion, amyloid-β (Αβ) plaques in the cortex and hippocampus, and exacerbated inflammatory responses. Recent studies have shown that these neuropathological features could be reversed by stem cell transplantation. However, the effects induced by neural (NSC) and mesenchymal (MSC) stem cells has never been compared in an AD animal model. Therefore, the present study aimed to investigate whether transplantation of NSC or MSC into the hippocampus of APP/PS1 mice reverses AD-induced pathological alterations, evaluated by the locomotor activity (open field test), short- and long-term memory (object recognition) tests, Αβ plaques (6-E10), microglia distribution (Iba-1), M1 (iNOS) and M2 (ARG-1) microglial phenotype frequencies. NSC and MSC engraftment reduced the number of Αβ plaques and produced an increase in M2 microglia polarization in the hippocampus of APP/PS1 mice, suggesting an anti-inflammatory effect of stem cell transplantation. NSC also reversed the hyperlocomotor activity and increased the number of microglia in the hippocampus of APP/PS1 mice. No impairment of short or long-term memory was observed in APP/PS1 mice. Overall, this study highlights the potential beneficial effects of transplanting NSC or MSC for AD treatment.

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Acknowledgements

We acknowledge the CEDEME animal facility (Centro de Desenvolvimento de Modelos Experimentais para Biologia e Medicina) for providing us with the double-transgenic APPswe/PS1dE9 mice.

Funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES)—Finance Code 001, scholarship 88882.330549/2019–01, as well as by the São Paulo Research Foundation (FAPESP project No. 2017/12412–2 awarded to BML and 2018/07366–4 awarded to HU), the National Council for Scientific and Technological Development (CNPq), the Project First-Class Disciplines Development of Chengdu University of Traditional Chinese Medicine (CZYHW1901), and Science & Technology Program of Sichuan Province, China (2019YFH0108).

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Authors and Affiliations

  1. Laboratório de Neurofisiologia, Depto. Fisiologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil

    Henrique C. Campos, Debora Hashiguchi, Deborah Y. Hukuda, Christiane Gimenes, Simone A. A. Romariz & Beatriz Monteiro Longo

  2. Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, SP, Brazil

    Deidiane Elisa Ribeiro, Qing Ye & Henning Ulrich

  3. Laboratório de Plasticidade Sináptica, Brain Institute, Federal University of Rio Grande do Norte, Natal, RN, 59078-900, Caixa Postal: 1524, Brazil

    Debora Hashiguchi

  4. International Collaborative Centre On Big Science Plan for Purinergic Signalling, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China

    Qing Ye, Yong Tang & Henning Ulrich

  5. Acupuncture and Chronobiology Key Laboratory of Sichuan Province, Chengdu, 610075, China

    Qing Ye & Yong Tang

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  1. Henrique C. Campos
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  2. Deidiane Elisa Ribeiro
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  9. Henning Ulrich
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  10. Beatriz Monteiro Longo
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Contributions

Henrique Correia Campos conducted the experiments and wrote the manuscript; Deidiane Elisa Ribeiro conducted the experiments, data analysis and wrote the manuscript; Debora Hashiguchi performed experiments, data analysis and revised the paper; Deborah Y Hukuda performed experiments and analysis; Christiane Gimenes performed experiments; Simone A A Romariz performed experiments and statistical analysis, designed figures and wrote the paper; Qing Ye contributed to data analysis and revised the manuscript; Yong Tang contributed to the construction of the manuscript and revised the paper; Henning Ulrich provided financing, assisted with the use of the TissueFAXS cytometer, contributed to writing and revised the manuscript, and Beatriz Monteiro Longo supervised the work, wrote and revised the manuscript.

Corresponding author

Correspondence to Beatriz Monteiro Longo.

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Ethical Approval

All the procedures followed the Ethical Guidelines for the Use of Animals and were approved by the local commission (Comissão de Ética no Uso de Animais, Universidade Federal de São Paulo), process nº 9268250618, and the National Council for Scientific and Technological Development (CNPq).

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Not applicable.

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All authors have approved the final version of the manuscript.

Competing Interests

H.U. declares consulting activities for TissueGnostics GmbH, Vienna, Austria. The authors declare that they have no competing interests.

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This article is part of the Topical Collection on Special issue on Neurogenesis and Neurodegeneration: Basic Research and Clinic Applications

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Campos, H.C., Ribeiro, D.E., Hashiguchi, D. et al. Distinct Effects of the Hippocampal Transplantation of Neural and Mesenchymal Stem Cells in a Transgenic Model of Alzheimer’s Disease. Stem Cell Rev and Rep 18, 781–791 (2022). https://doi.org/10.1007/s12015-021-10321-9

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  • DOI: https://doi.org/10.1007/s12015-021-10321-9

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