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Title: Effect of systemic transplantation of bone marrow-derived mesenchymal stem cells on neuropathology markers in APP/PS1 Alzheimer mice
Authors: Naaldijk, Yahaira
Jaeger, Carsten
Fabian, Claire
Leovsky, Christiane
Blüher, A.
Rudolph, Lukas
Hinze, Arnd
Stolzing, Alexandra
Keywords: Amyloid
Mesenchymal stem cells
Alzheimer’s disease
Issue Date: 2016
Publisher: © John Wiley and Sons
Citation: NAALDIJK, Y. ... et al., 2016. Effect of systemic transplantation of bone marrow-derived mesenchymal stem cells on neuropathology markers in APP/PS1 Alzheimer mice. Neuropathology and Applied Neurobiology, DOI: 10.1111/nan.12319.
Abstract: Mesenchymal stem cells (MSC) have recently attracted interest as a potential basis for a cell based therapy of AD. We investigated the putative immune-modulatory effects in neuroinflammation of systemic transplantation of MSC into APP/PS1 transgenic mice.10(6) MSC were injected into APP/PS1 mice via the tail vein and histological analysis was performed for microglia and amyloid (pE3-A[beta]) plaque numbers, glial distribution and pE3-A[beta] plaque size. In addition, a biochemical analysis by qPCR for pro-inflammatory, chemoattractant and neurotrophic factors was performed.MSC co-localized with pE3-A[beta] plaques. The effects of transplantation on microglia-associated pathology could be observed after 28 hours. Animals showed a reduction in microglial numbers in the cortex and in size. Gene expression was reduced for TNF-[alpha], IL-6, MCP-1, and for NGF, in MSC recipients. Also, we investigated for the first time and found no changes in expression of IL-10, CCR5, BDNF, VEGF and IFN[gamma]. PTGER2 expression levels were increased in the hippocampus but were reduced in the cortex of MSC recipients. While there were no transplant-related changes in pE3-A[beta] plaque numbers, a reduction in the size of pE3-A[beta] plaques was observed in the hippocampus of transplant recipients.This is the first study to show reduction in pE3-A[beta] plaque size. pE3-A[beta] plaques have gained attention as potential key participants in AD due to their increased aggregation propensity, the possibility for the initial seeding event, resistance against degradation and neurotoxicity. These findings support the hypothesis that MSC-transplants may affect AD pathology via an immune modulatory function that includes an effect on microglial cells.
Description: This document will remain Closed Access until twelve months after the date of its commercial publication.
Sponsor: The work presented in this paper was made possible by funding from the German Federal Ministry of Education and Research (BMBF 1315883), Fraunhofer Society and Dan Stoicescu as well as Longecity funding. We thank Dr. Markus Morawski from the Paul Flechsig Institute for Brain research for providing eGFP transgenic mice as bone marrow donors. Special thanks for Dr. Sebastian Sethe for comments and critical reading.
Version: Accepted for publication
DOI: 10.1111/nan.12319
URI: https://dspace.lboro.ac.uk/2134/20646
Publisher Link: http://dx.doi.org/10.1111/nan.12319
ISSN: 0305-1846
Appears in Collections:Closed Access (Mechanical, Electrical and Manufacturing Engineering)

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