Título:	GVHD-derived plasma as a priming strategy of mesenchymal stem cells
Autor(es):	Carvalho, Amandda Évelin Silva Rodrigues, Leane Perim Schiavinato, Josiane Lilian Alborghetti, Marcos Rodrigo Bettarello, Gustavo Simões, Belinda Pinto Neves, Francisco de Assis Rocha Panepucci, Rodrigo Alexandre Carvalho, Juliana Lott de Araujo, Felipe Saldanha de
Assunto:	Células-tronco mesenquimais Linfócitos Doença do enxerto contra hospedeiro Imunomodulação
Data de publicação:	16-Abr-2020
Editora:	BMC
Referência:	SILVA-CARVALHO, Amandda Évelin Silva et al. GVHD-derived plasma as a priming strategy of mesenchymal stem cells. Stem Cell Research & Therapy, v. 11, 156, 2020. DOI: https://doi.org/10.1186/s13287-020-01659-x. Disponível em: https://stemcellres.biomedcentral.com/articles/10.1186/s13287-020-01659-x. Acesso em: 13 out. 2020.
Abstract:	Background: Mesenchymal stem cell (MSC) therapy is an important alternative for GVHD treatment, but a third of patients fail to respond to such therapy. Therefore, strategies to enhance the immunosuppressive potential of MSCs constitute an active area of investigation. Here, we proposed an innovative priming strategy based on the plasma obtained from GVHD patients and tested whether this approach could enhance the immunosuppressive capacity of MSCs. Methods: We obtained the plasma from healthy as well as acute (aGVHD) and chronic (cGVHD) GVHD donors. Plasma samples were characterized according to the TNF-α, IFN-γ, IL-10, IL-1β, IL-12p40, and IL-15 cytokine levels. The MSCs primed with such plasmas were investigated according to surface markers, morphology, proliferation, mRNA expression, and the capacity to control T cell proliferation and Treg generation. Results: Interestingly, 57% of aGVHD and 33% of cGVHD plasmas significantly enhanced the immunosuppressive potential of MSCs. The most suppressive MSCs presented altered morphology, and those primed with cGHVD displayed a pronounced overexpression of ICAM-1 on their surface. Furthermore, we observed that the ratio of IFN-γ to IL-10 cytokine levels in the plasma used for MSC priming was significantly correlated with higher suppressive potential and Treg generation induction by primed MSCs, regardless of the clinical status of the donor. Conclusions: This work constitutes an important proof of concept which demonstrates that it is possible to prime MSCs with biological material and also that the cytokine levels in the plasma may affect the MSC immunosuppressive potential, serving as the basis for the development of new therapeutic approaches for the treatment of immune diseases.
Licença:	© The Author(s). 2020 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
DOI:	https://doi.org/10.1186/s13287-020-01659-x
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