{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T22:53:29Z","timestamp":1788994409571,"version":"build-2803163510"},"reference-count":101,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Higher Education and Science of the Republic of Kazakhstan","award":["AP23485236"],"award-info":[{"award-number":["AP23485236"]}]},{"name":"Ministry of Higher Education and Science of the Republic of Kazakhstan","award":["BR24992841"],"award-info":[{"award-number":["BR24992841"]}]},{"name":"Ministry of Higher Education and Science of the Republic of Kazakhstan","award":["H2020-MSCA-RISE-2020"],"award-info":[{"award-number":["H2020-MSCA-RISE-2020"]}]},{"name":"Ministry of Higher Education and Science of the Republic of Kazakhstan","award":["101007642"],"award-info":[{"award-number":["101007642"]}]},{"name":"PhytoApp EU framework","award":["AP23485236"],"award-info":[{"award-number":["AP23485236"]}]},{"name":"PhytoApp EU framework","award":["BR24992841"],"award-info":[{"award-number":["BR24992841"]}]},{"name":"PhytoApp EU framework","award":["H2020-MSCA-RISE-2020"],"award-info":[{"award-number":["H2020-MSCA-RISE-2020"]}]},{"name":"PhytoApp EU framework","award":["101007642"],"award-info":[{"award-number":["101007642"]}]},{"name":"European Union","award":["AP23485236"],"award-info":[{"award-number":["AP23485236"]}]},{"name":"European Union","award":["BR24992841"],"award-info":[{"award-number":["BR24992841"]}]},{"name":"European Union","award":["H2020-MSCA-RISE-2020"],"award-info":[{"award-number":["H2020-MSCA-RISE-2020"]}]},{"name":"European Union","award":["101007642"],"award-info":[{"award-number":["101007642"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Neuroinflammation is a key feature of Alzheimer\u2019s 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-1\u03b2, Il-6, Cd45, Tnf) and plasticity markers (Tub\u03b23, 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 &lt;100 \u03bcm2. 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.<\/jats:p>","DOI":"10.3390\/cells14151168","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T16:16:10Z","timestamp":1753805770000},"page":"1168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["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"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7583-1464","authenticated-orcid":false,"given":"Johannes","family":"de Munter","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Neuropsychology, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Neuroplast B.V., 6222 NK Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0258-1879","authenticated-orcid":false,"given":"Kirill","family":"Chaprov","sequence":"additional","affiliation":[{"name":"Neuroplast B.V., 6222 NK Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3295-8763","authenticated-orcid":false,"given":"Ekkehard","family":"Lang","sequence":"additional","affiliation":[{"name":"Neuroplast B.V., 6222 NK Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kseniia","family":"Sitdikova","sequence":"additional","affiliation":[{"name":"Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4411-6892","authenticated-orcid":false,"given":"Erik Ch.","family":"Wolters","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3501-574X","authenticated-orcid":false,"given":"Evgeniy","family":"Svirin","sequence":"additional","affiliation":[{"name":"Neuroplast B.V., 6222 NK Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3670-3600","authenticated-orcid":false,"given":"Aliya","family":"Kassenova","sequence":"additional","affiliation":[{"name":"Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3818-3079","authenticated-orcid":false,"given":"Andrey","family":"Tsoy","sequence":"additional","affiliation":[{"name":"Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7682-2591","authenticated-orcid":false,"given":"Boris W.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Neuroplast B.V., 6222 NK Maastricht, The Netherlands"},{"name":"Department of Neonatology, Poznan University of Medical Sciences, 60806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6161-1671","authenticated-orcid":false,"given":"Sholpan","family":"Askarova","sequence":"additional","affiliation":[{"name":"Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Careen A.","family":"Schroeter","sequence":"additional","affiliation":[{"name":"Preventive and Environmental Medicine, Kastanienhof Clinic, 50858 Cologne-Junkersdorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1380-6655","authenticated-orcid":false,"given":"Daniel C.","family":"Anthony","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana","family":"Strekalova","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuropsychology, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Beata, B.-K., Wojciech, J., Johannes, K., Piotr, L., and Barbara, M. 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