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

Author(s)

Campos, Henrique C. ^[1] ; Ribeiro, Deidiane Elisa ^[2] ; Hashiguchi, Debora ^{[1, 3]} ; Hukuda, Deborah Y. ^[1] ; Gimenes, Christiane ^[1] ; Romariz, Simone A. A. ^[1] ; Ye, Qing ^{[2, 4, 5]} ; Tang, Yong ^{[4, 5]} ; Ulrich, Henning ^{[2, 4]} ; Longo, Beatriz Monteiro ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Fisiol, Lab Neurofisiol, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo, SP - Brazil

^[3] Univ Fed Rio Grande do Norte, Brain Inst, Lab Plasticidade Sinapt, Caixa Postal 1524, BR-59078900 Natal, RN - Brazil

^[4] Chengdu Univ Tradit Chinese Med, Int Collaborat Ctr Big Sci Plan Purinerg Signalli, Chengdu 610075 - Peoples R China

^[5] Acupuncture & Chronobiol Key Lab Sichuan Prov, Chengdu 610075 - Peoples R China

• Document type: Journal article
• Source: STEM CELL REVIEWS AND REPORTS; JAN 2022.
• Web of Science Citations: 0

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-beta (A beta) 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, A beta plaques (6-E10), microglia distribution (Iba-1), M1 (iNOS) and M2 (ARG-1) microglial phenotype frequencies. NSC and MSC engraftment reduced the number of A beta 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. (AU)

• FAPESP's process: 17/12412-2 - Degenerative and regenerative processes in Alzheimer's Disease: from cell culture to cell therapy
• Grantee: Beatriz de Oliveira Monteiro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Research Projects - Thematic Grants