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Dynamic Changes in Brain Mesenchymal Perivascular Cells Associate with Multiple Sclerosis Disease Duration, Active Inflammation, and Demyelination

Iacobaeus, E; Sugars, RV; Andren, AT; Alm, JJ; Qian, H; Frantzen, J; Newcombe, J; ... Le Blanc, K; + view all (2017) Dynamic Changes in Brain Mesenchymal Perivascular Cells Associate with Multiple Sclerosis Disease Duration, Active Inflammation, and Demyelination. Stem Cells Translational Medicine , 6 (10) pp. 1840-1851. 10.1002/sctm.17-0028. Green open access

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Abstract

Vascular changes, including blood brain barrier destabilization, are common pathological features in multiple sclerosis (MS) lesions. Blood vessels within adult organs are reported to harbor mesenchymal stromal cells (MSCs) with phenotypical and functional characteristics similar to pericytes. We performed an immunohistochemical study of MSCs/pericytes in brain tissue from MS and healthy persons. Post-mortem brain tissue from patients with early progressive MS (EPMS), late stage progressive MS (LPMS), and healthy persons were analyzed for the MSC and pericyte markers CD146, platelet-derived growth factor receptor beta (PDGFRβ), CD73, CD271, alpha-smooth muscle actin, and Ki67. The MS samples included active, chronic active, chronic inactive lesions, and normal-appearing white matter. MSC and pericyte marker localization were detected in association with blood vessels, including subendothelial CD146+PDGFRβ+Ki67+ cells and CD73+CD271+PDGFRβ+Ki67– cells within the adventitia and perivascular areas. Both immunostained cell subpopulations were termed mesenchymal perivascular cells (MPCs). Quantitative analyses of immunostainings showed active lesions containing increased regions of CD146+PDGFRβ+Ki67+ and CD73+CD271+PDGFRβ+Ki67– MPC subpopulations compared to inactive lesions. Chronic lesions presented with decreased levels of CD146+PDGFRβ+Ki67+ MPC cells compared to control tissue. Furthermore, LPMS lesions displayed increased numbers of blood vessels harboring greatly enlarged CD73+CD271+ adventitial and perivascular areas compared to control and EPMS tissue. In conclusion, we demonstrate the presence of MPC subgroups in control human brain vasculature, and their phenotypic changes in MS brain, which correlated with inflammation, demyelination and MS disease duration. Our findings demonstrate that brain-derived MPCs respond to pathologic mechanisms involved in MS disease progression and suggest that vessel-targeted therapeutics may benefit patients with progressive MS.

Type: Article
Title: Dynamic Changes in Brain Mesenchymal Perivascular Cells Associate with Multiple Sclerosis Disease Duration, Active Inflammation, and Demyelination
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/sctm.17-0028
Publisher version: http://dx.doi.org/10.1002/sctm.17-0028
Language: English
Additional information: © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Keywords: Science & Technology, Life Sciences & Biomedicine, Cell & Tissue Engineering, Cell Biology, Multiple sclerosis, Neuroinflammation, Central nervous system, Mesenchymal stromal cell, Pericyte, Perivascular niche, Blood vessels, EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, CENTRAL-NERVOUS-SYSTEM, ADULT HUMAN BRAIN, STEM-CELLS, STROMAL CELLS, MICROVASCULAR PERICYTES, IN-VIVO, BARRIER, EXPRESSION, PHENOTYPE
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10030565
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