T cell immunomodulation by clinically used allogeneic human cancellous bone fragments: a potential novel immunotherapy tool

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El-Sherbiny, YM ORCID: https://orcid.org/0000-0003-4791-3475, El-Jawhari, JJ, Moseley, TA, McGonagle, D and Jones, E, 2018. T cell immunomodulation by clinically used allogeneic human cancellous bone fragments: a potential novel immunotherapy tool. Scientific Reports, 8: 13535. ISSN 2045-2322

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Official URL: http://doi.org/10.1038/s41598-018-31979-1

Abstract

Multipotential stromal cells (MSCs) demonstrate strong immunomodulation capabilities following culture expansion. We have previously demonstrated that human cancellous bone fragments (CBFs) clinically used as viable allografts for spinal fusion have resident MSCs that exhibit T cell immunomodulation after monolayer expansion. This study investigated the immunomodulatory ability of these CBFs without MSC culture-expansion. CD4 positive T cells were induced to proliferate using CD3/CD28 stimulation and added to CBFs at diferent ratios of T cells per gram of CBF. A dosedependent suppressive efect on T cell proliferation was evident and correlated with increased culture supernatant levels of TGF-ß1, but not PGE2. CBF-driven immunosuppression was reduced in co-cultures with TGF-ß neutralising antibodies and was higher in cell contact compared to non-contact cultures. CBF gene expression profle identifed vascular cell adhesion molecule-1, bone marrow stromal antigen 2/CD317 and other interferon signalling pathway members as potential immunomodulatory mediators. The CD317 molecule was detected on the surface of CBF-resident cells confrming the gene expression data. Taken together, these data demonstrate that human clinically used CBFs are inherently immunomodulatory and suggest that these viable allografts may be used to deliver therapeutic immunomodulation for immune-related diseases.

Item Type:	Journal article
Publication Title:	Scientific Reports
Creators:	El-Sherbiny, Y.M., El-Jawhari, J.J., Moseley, T.A., McGonagle, D. and Jones, E.
Publisher:	Nature Publishing Group
Date:	10 September 2018
Volume:	8
ISSN:	2045-2322
Identifiers:	Number Type 10.1038/s41598-018-31979-1 DOI 31979 Publisher Item Identifier
Rights:	© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Divisions:	Schools > School of Science and Technology
Record created by:	Jill Tomkinson
Date Added:	06 Feb 2019 11:08
Last Modified:	06 Feb 2019 11:09
URI:	https://irep.ntu.ac.uk/id/eprint/35770