Corbett, Jennifer M. and Hawthorne, Ian and Dunbar, Hazel and Coulter, Ivan and Chonghaile, Mairead Ni and Flynn, Catherine M. and English, Karen (2021) Cyclosporine A and IFNγ licencing enhances human mesenchymal stromal cell potency in a humanised mouse model of acute graft versus host disease. Stem Cell Research & Therapy, 12 (238). pp. 1-10. ISSN 1757-6512

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Abstract

Immunosuppressive ability in human MSC donors has been shown to be variable and may be a limiting factor in MSC therapeutic efficacy in vivo. The importance of cytokine activation of mesenchymal stromal cells (MSCs) to facilitate their immunosuppressive function is well established. This study sought to further understand the interactions between MSCs and the commonly used calcineurin inhibitor cyclosporine A (CsA). The existing literature regarding approaches that use MSCs and cyclosporine are conflicting regarding the effect of CsA on MSC potency and function. Here, we clearly demonstrate that when added at the same time as MSCs, CsA negatively affects MSC suppression of T cell proliferation. However, licencing MSCs with IFNγ before addition of CsA protects MSCs from this negative effect. Notably, adding CsA to MSCs after IFNγ pre-stimulation enhances MSC production of IDO. Mechanistically, we identified that CsA reduces SOCS1 expression to facilitate enhanced IDO production in IFNγ pre-stimulated MSCs. Importantly, CsA exposure to IFNγ pre-stimulated MSC before administration, significantly enhanced the potency of MSCs in a human relevant humanised mouse model of acute Graft versus Host Disease. In summary, this study identified a novel licencing strategy to enhance MSC potency in vitro and in vivo.

Item Type:	Article
Keywords:	MSC cell therapy; Immunosuppressive drugs; Cyclosporine A; IFNγ; GvHD; SOCS1;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	16208
Identification Number:	https://doi.org/10.1186/s13287-021-02309-6
Depositing User:	Karen English
Date Deposited:	29 Jun 2022 10:06
Journal or Publication Title:	Stem Cell Research & Therapy
Publisher:	BMC
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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