Neuro-Cells Mitigate Amyloid Plaque Formation and Behavioral Deficits in the APPswe/PS1dE9 Model of Alzheimer Disease While Also Reducing IL-6 Production in Human Monocytes
de Munter J. Chaprov K. Lang E. Sitdikova K. Wolters E.C. Svirin E. Kassenova A. Tsoy A. Kramer B.W. Askarova S. Schroeter C.A. Anthony D.C. Strekalova T.
August 2025Multidisciplinary Digital Publishing Institute (MDPI)
Cells
2025#14Issue 15
Neuroinflammation is a key feature of Alzheimer’s disease (AD), and stem cell therapies have emerged as promising candidates due to their immunomodulatory properties. Neuro-Cells (NC), a combination of unmodified mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs), have demonstrated therapeutic potential in models of central nervous system (CNS) injury and neurodegeneration. Here, we studied the effects of NC in APPswe/PS1dE9 mice, an AD mouse model. Twelve-month-old APPswe/PS1dE9 mice or their wild-type littermates were injected with NC or vehicle into the cisterna magna. Five to six weeks post-injection, cognitive, locomotor, and emotional behaviors were assessed. The brain was stained for amyloid plaque density using Congo red, and for astrogliosis using DAPI and GFAP staining. Gene expression of immune activation markers (Il-1β, Il-6, Cd45, Tnf) and plasticity markers (Tubβ3, Bace1, Trem2, Stat3) was examined in the prefrontal cortex. IL-6 secretion was measured in cultured human monocytes following endotoxin challenge and NC treatment. Untreated APPswe/PS1dE9 mice displayed impaired learning in the conditioned taste aversion test, reduced object exploration, and anxiety-like behavior, which were improved in the NC-treated mutants. NC treatment normalized the expression of several immune and plasticity markers and reduced the density of GFAP-positive cells in the hippocampus and thalamus. NC treatment decreased amyloid plaque density in the hippocampus and thalamus, targeting plaques of <100 μm2. Additionally, NC treatment suppressed IL-6 secretion by human monocytes. Thus, NC treatment alleviated behavioral deficits and reduced amyloid plaque formation in APPswe/PS1dE9 mice, likely via anti-inflammatory mechanisms. The reduction in IL-6 production in human monocytes further supports the potential of NC therapy for the treatment of AD.
Alzheimer’s disease , amyloid plaques , APPswe/PS1dE9 mice , cognition , cytokines , emotionality , neuroinflammation , stem cell therapy
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Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, 6229 ER, Netherlands
Neuroplast B.V, Maastricht, 6222 NK, Netherlands
Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, 010000, Kazakhstan
Department of Neurology, University of Zurich, Zurich, 8091, Switzerland
Department of Neonatology, Poznan University of Medical Sciences, Poznan, 60806, Poland
Preventive and Environmental Medicine, Kastanienhof Clinic, Junkersdorf, Cologne, 50858, Germany
Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, United Kingdom
Department of Psychiatry and Neuropsychology
Neuroplast B.V
Center for Life Sciences
Department of Neurology
Department of Neonatology
Preventive and Environmental Medicine
Department of Pharmacology
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