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Mesenchymal Stromal Cells Protect Endothelial Cells from Cytotoxic T Lymphocyte-Induced Lysis
Alternative Title
Mesenchymal Stem Cells Protect Endothelial Cells from Cytotoxic T Lymphocyte-Induced Lysis
Date Issued
2016-08-24
Date Available
2017-12-19T13:03:37Z
Abstract
The integrity of the vasculature plays an important role in the success ofallogeneic organ and haematopoietic stem cell transplantation. Endothelial cells(EC) have previously been shown to be the target of activated cytotoxic Tlymphocytes (CTL) resulting in extensive cell lysis. Mesenchymal stromal cells(MSC) are multipotent cells which can be isolated from multiple sites, eachdemonstrating immunomodul atory capabilities. They are explored herein fortheir potential to protect EC from CTL-targeted lys is. CD8+T cells isolated fromhuman PBMC were stimulated with mitotically inactive cells of a humanmicrovascular endothelial cell line (CDC/EU.HMEC-1, further referred to asHMEC) for 7 days. Target HMEC were cultured in the presence or absence ofMSC for 24 h before exposure to activated allogeneic CTL for 4 h. EC were thenanalysed for cytotoxic lysis by flow cytometry. Culture of HMEC with MSC inthe efferent immune phase (24 h before the assay) led to a decrease in HMEClysis. This lysis was determined to be MHC Class I restricted linked and furtheranalysis suggested that MSC contact is important in abrogation of lysis, asprotection is reduced where MSC are separated in transwell experiments. Theefficacy of multiple sources of MSC was also confirmed, and the collaborativeeffect of MSC and the endothelium protective drug defibrotide were determined,with defibrotide enhancing the protection provided by MSC. These resultssupport the use of MSC as an adjuvant cellular therapeutic in transplantmedicine, alone or in conjunction with EC protective agents such as defibrotide.
Sponsorship
Science Foundation Ireland
Other Sponsorship
Bayerische Forschungsstiftung (Bavarian Research Foundation)
Wilhelm Sander Foundation
Servier Laboratories
Type of Material
Journal Article
Publisher
Wiley
Journal
Scandinavian Journal of Immunology
Volume
84
Issue
3
Start Page
158
End Page
164
Copyright (Published Version)
2016 the Foundation for the Scandanavian Journal of Immunology
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
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Mesenchymal stem cells protect endothelial cells from cytotoxic T lymphocyte induced lysis-1.pdf
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