Therapeutic Effects of Neuro-Cells on Amyloid Pathology, BDNF Levels, and Insulin Signalling in APPswe/PSd1E9 Mice
de Munter J.P.J.M. Tsoy A. Sitdikova K. Wolters E.C. Chaprov K. Yenkoyan K.B. Torosyan H. Askarova S. Anthony D.C. Strekalova T.
August 2025Multidisciplinary Digital Publishing Institute (MDPI)
Cells
2025#14Issue 16
Stem cell therapies, including mesenchymal (MSCs) and haematopoietic stem cells (HSCs), have shown promise in neurodegenerative diseases. Here, we investigated the therapeutic effects of a defined combination of unmanipulated MSCs and CD34+ HSCs, termed Neuro-Cells (NC), in a murine model of Alzheimer’s disease (AD), the APPswe/PS1dE9 mouse. At 12 months of age, mice received intracisternal injections of NC (1.39 × 106 MSCs + 5 × 105 HSCs) or vehicle. After 45 days, behavioural testing, immunohistochemical analyses of amyloid plaque density (APD), and cortical gene expression profiling were conducted. NC-treated APP/PS1 mice exhibited preserved object recognition memory and reduced anxiety-like behaviours, contrasting with deficits observed in untreated transgenic controls. Histologically, NC treatment significantly reduced the density of small amyloid plaques (<50 μm2) in the hippocampus and thalamus, and total plaque burden in the thalamus. Gene expression analysis revealed that NC treatment normalised or reversed disease-associated changes in insulin receptor (IR) signalling and neurotrophic pathways. Specifically, NC increased expression of Bdnf, Irs2, and Pgc-1α, while attenuating aberrant upregulation of Insr, Igf1r, and markers of ageing and AD-related pathology (Sirt1, Gdf15, Arc, Egr1, Cldn5). These findings indicate that NC therapy mitigates behavioural and molecular hallmarks of AD, potentially via restoration of BDNF and insulin receptor-mediated signalling.
Alzheimer’s disease , amyloid plaques , APP/PS1 mice , cognition , emotionality , haematopoietic stem cells (HSCs) , insulin receptor , mesenchymal stem cells (MSCs) , neurotrophins , 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
Neuroscience Laboratory, COBRAIN Center, Yerevan State Medical University, Yerevan, 0025, Armenia
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
Neuroscience Laboratory
Department of Pharmacology
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