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Dichotomic Potency of IFNγ Licensed Allogeneic Mesenchymal Stromal Cells in Animal Models of Acute Radiation Syndrome and Graft Versus Host Disease

Mesenchymal stromal cells (MSCs) are being tested as a cell therapy in clinical trials for dozens of inflammatory disorders, with varying levels of efficacy reported. Suitable and robust preclinical animal models for testing the safety and efficacy of different types of MSC products before use in cl...

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Autores principales: Chinnadurai, Raghavan, Bates, Paul D., Kunugi, Keith A., Nickel, Kwangok P., DeWerd, Larry A., Capitini, Christian M., Galipeau, Jacques, Kimple, Randall J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352793/
https://www.ncbi.nlm.nih.gov/pubmed/34386012
http://dx.doi.org/10.3389/fimmu.2021.708950
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author Chinnadurai, Raghavan
Bates, Paul D.
Kunugi, Keith A.
Nickel, Kwangok P.
DeWerd, Larry A.
Capitini, Christian M.
Galipeau, Jacques
Kimple, Randall J.
author_facet Chinnadurai, Raghavan
Bates, Paul D.
Kunugi, Keith A.
Nickel, Kwangok P.
DeWerd, Larry A.
Capitini, Christian M.
Galipeau, Jacques
Kimple, Randall J.
author_sort Chinnadurai, Raghavan
collection PubMed
description Mesenchymal stromal cells (MSCs) are being tested as a cell therapy in clinical trials for dozens of inflammatory disorders, with varying levels of efficacy reported. Suitable and robust preclinical animal models for testing the safety and efficacy of different types of MSC products before use in clinical trials are rare. We here introduce two highly robust animal models of immune pathology: 1) acute radiation syndrome (ARS) and 2) graft versus host disease (GvHD), in conjunction with studying the immunomodulatory effect of well-characterized Interferon gamma (IFNγ) primed bone marrow derived MSCs. The animal model of ARS is based on clinical grade dosimetry precision and bioluminescence imaging. We found that allogeneic MSCs exhibit lower persistence in naïve compared to irradiated animals, and that intraperitoneal infusion of IFNγ prelicensed allogeneic MSCs protected animals from radiation induced lethality by day 30. In direct comparison, we also investigated the effect of IFNγ prelicensed allogeneic MSCs in modulating acute GvHD in an animal model of MHC major mismatched bone marrow transplantation. Infusion of IFNγ prelicensed allogeneic MSCs failed to mitigate acute GvHD. Altogether our results demonstrate that infused IFNγ prelicensed allogeneic MSCs protect against lethality from ARS, but not GvHD, thus providing important insights on the dichotomy of IFNγ prelicensed allogenic MSCs in well characterized and robust animal models of acute tissue injury.
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spelling pubmed-83527932021-08-11 Dichotomic Potency of IFNγ Licensed Allogeneic Mesenchymal Stromal Cells in Animal Models of Acute Radiation Syndrome and Graft Versus Host Disease Chinnadurai, Raghavan Bates, Paul D. Kunugi, Keith A. Nickel, Kwangok P. DeWerd, Larry A. Capitini, Christian M. Galipeau, Jacques Kimple, Randall J. Front Immunol Immunology Mesenchymal stromal cells (MSCs) are being tested as a cell therapy in clinical trials for dozens of inflammatory disorders, with varying levels of efficacy reported. Suitable and robust preclinical animal models for testing the safety and efficacy of different types of MSC products before use in clinical trials are rare. We here introduce two highly robust animal models of immune pathology: 1) acute radiation syndrome (ARS) and 2) graft versus host disease (GvHD), in conjunction with studying the immunomodulatory effect of well-characterized Interferon gamma (IFNγ) primed bone marrow derived MSCs. The animal model of ARS is based on clinical grade dosimetry precision and bioluminescence imaging. We found that allogeneic MSCs exhibit lower persistence in naïve compared to irradiated animals, and that intraperitoneal infusion of IFNγ prelicensed allogeneic MSCs protected animals from radiation induced lethality by day 30. In direct comparison, we also investigated the effect of IFNγ prelicensed allogeneic MSCs in modulating acute GvHD in an animal model of MHC major mismatched bone marrow transplantation. Infusion of IFNγ prelicensed allogeneic MSCs failed to mitigate acute GvHD. Altogether our results demonstrate that infused IFNγ prelicensed allogeneic MSCs protect against lethality from ARS, but not GvHD, thus providing important insights on the dichotomy of IFNγ prelicensed allogenic MSCs in well characterized and robust animal models of acute tissue injury. Frontiers Media S.A. 2021-07-26 /pmc/articles/PMC8352793/ /pubmed/34386012 http://dx.doi.org/10.3389/fimmu.2021.708950 Text en Copyright © 2021 Chinnadurai, Bates, Kunugi, Nickel, DeWerd, Capitini, Galipeau and Kimple https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Immunology
Chinnadurai, Raghavan
Bates, Paul D.
Kunugi, Keith A.
Nickel, Kwangok P.
DeWerd, Larry A.
Capitini, Christian M.
Galipeau, Jacques
Kimple, Randall J.
Dichotomic Potency of IFNγ Licensed Allogeneic Mesenchymal Stromal Cells in Animal Models of Acute Radiation Syndrome and Graft Versus Host Disease
title Dichotomic Potency of IFNγ Licensed Allogeneic Mesenchymal Stromal Cells in Animal Models of Acute Radiation Syndrome and Graft Versus Host Disease
title_full Dichotomic Potency of IFNγ Licensed Allogeneic Mesenchymal Stromal Cells in Animal Models of Acute Radiation Syndrome and Graft Versus Host Disease
title_fullStr Dichotomic Potency of IFNγ Licensed Allogeneic Mesenchymal Stromal Cells in Animal Models of Acute Radiation Syndrome and Graft Versus Host Disease
title_full_unstemmed Dichotomic Potency of IFNγ Licensed Allogeneic Mesenchymal Stromal Cells in Animal Models of Acute Radiation Syndrome and Graft Versus Host Disease
title_short Dichotomic Potency of IFNγ Licensed Allogeneic Mesenchymal Stromal Cells in Animal Models of Acute Radiation Syndrome and Graft Versus Host Disease
title_sort dichotomic potency of ifnγ licensed allogeneic mesenchymal stromal cells in animal models of acute radiation syndrome and graft versus host disease
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352793/
https://www.ncbi.nlm.nih.gov/pubmed/34386012
http://dx.doi.org/10.3389/fimmu.2021.708950
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