Kay, AG, Fox, JM, Hewitson, JP et al. (7 more authors) (2022) CD317-Positive Immune Stromal Cells in Human “Mesenchymal Stem Cell” Populations. Frontiers in Immunology, 13. 903796. ISSN 1664-3224
Abstract
Heterogeneity of bone marrow mesenchymal stromal cells (MSCs, frequently referred to as “mesenchymal stem cells”) clouds biological understanding and hampers their clinical development. In MSC cultures most commonly used in research and therapy, we have identified an MSC subtype characterized by CD317 expression (CD317pos (29.77 ± 3.00% of the total MSC population), comprising CD317dim (28.10 ± 4.60%) and CD317bright (1.67 ± 0.58%) MSCs) and a constitutive interferon signature linked to human disease. We demonstrate that CD317pos MSCs induced cutaneous tissue damage when applied a skin explant model of inflammation, whereas CD317neg MSCs had no effect. Only CD317neg MSCs were able to suppress proliferative cycles of activated human T cells in vitro, whilst CD317pos MSCs increased polarization towards pro-inflammatory Th1 cells and CD317neg cell lines did not. Using an in vivo peritonitis model, we found that CD317neg and CD317pos MSCs suppressed leukocyte recruitment but only CD317neg MSCs suppressed macrophage numbers. Using MSC-loaded scaffolds implanted subcutaneously in immunocompromised mice we were able to observe tissue generation and blood vessel formation with CD317neg MSC lines, but not CD317pos MSC lines. Our evidence is consistent with the identification of an immune stromal cell, which is likely to contribute to specific physiological and pathological functions and influence clinical outcome of therapeutic MSCs.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 Kay, Fox, Hewitson, Stone, Robertson, James, Wang, Kapasa, Yang and Genever. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
Keywords: | mesenchymal stromal cells, MSC subtypes, heterogeneity, immunomodulation, CD317, BST2, tetherin |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Dentistry (Leeds) > Oral Biology (Leeds) |
Funding Information: | Funder Grant number Royal Society IE110284 Royal Society IEC\NSFC\191344 |
Depositing User: | Symplectic Publications |
Date Deposited: | 17 Aug 2022 11:20 |
Last Modified: | 14 Feb 2024 11:57 |
Published Version: | https://www.frontiersin.org/journals/immunology/ar... |
Status: | Published |
Publisher: | Frontiers Media |
Identification Number: | 10.3389/fimmu.2022.903796 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:190051 |
Commentary/Response Threads
- Kay, AG, Fox, JM, Hewitson, JP, Stone, AP, Robertson, S, James, S, Wang, X-N, Kapasa, E, Yang, XB and Genever, PG CD317-Positive Immune Stromal Cells in Human “Mesenchymal Stem Cell” Populations. (deposited 17 Aug 2022 11:20) [Currently Displayed]
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