Prevention of non-infectious pulmonary complications after intra-bone marrow stem cell transplantation in mice
Non-infectious pulmonary complications including idiopathic pneumonia syndrome (IPS) and bronchiolitis obliterans syndrome (BOS), which are clinical and diagnostic manifestations of lung chronic graft-versus-host disease (GVHD), cause significant mortality after allogeneic stem cell transplantation...
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Public Library of Science (PLoS)
2022-01-01
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Series: | PLoS ONE |
Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9462704/?tool=EBI |
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author | Yoshiko Yamasuji-Maeda Hisakazu Nishimori Keisuke Seike Akira Yamamoto Hideaki Fujiwara Taiga Kuroi Kyosuke Saeki Haruko Fujinaga Sachiyo Okamoto Ken-ichi Matsuoka Nobuharu Fujii Takehiro Tanaka Masahiro Fujii Katsumi Mominoki Takuro Kanekura Yoshinobu Maeda |
author_facet | Yoshiko Yamasuji-Maeda Hisakazu Nishimori Keisuke Seike Akira Yamamoto Hideaki Fujiwara Taiga Kuroi Kyosuke Saeki Haruko Fujinaga Sachiyo Okamoto Ken-ichi Matsuoka Nobuharu Fujii Takehiro Tanaka Masahiro Fujii Katsumi Mominoki Takuro Kanekura Yoshinobu Maeda |
author_sort | Yoshiko Yamasuji-Maeda |
collection | DOAJ |
description | Non-infectious pulmonary complications including idiopathic pneumonia syndrome (IPS) and bronchiolitis obliterans syndrome (BOS), which are clinical and diagnostic manifestations of lung chronic graft-versus-host disease (GVHD), cause significant mortality after allogeneic stem cell transplantation (SCT). Increasing evidence suggests that alloantigen reactions in lung tissue play a central role in the pathogenesis of IPS and BOS; however, the mechanism is not fully understood. Several clinical and experimental studies have reported that intra-bone marrow (IBM)-SCT provides high rates of engraftment and is associated with a low incidence of acute GVHD. In the present study, allogeneic SCT was conducted in mouse models of IPS and BOS, to compare intravenous (IV)-SCT with IBM-SCT. Allogeneic IBM-SCT improved the clinical and pathological outcomes of pulmonary complications compared to those of IV-SCT. The mechanisms underlying the reductions in pulmonary complications in IBM-SCT mice were explored. The infiltrating lung cells were mainly CD11b+ myeloid and CD3+ T cells, in the same proportions as in transplanted donor cells. In an in vivo bioluminescence imaging, a higher proportion of injected donor cells was detected in the lung during the early phase (1 h after IV-SCT) than after IBM-SCT (16.7 ± 1.1 vs. 3.1 ± 0.7 × 105 photons/s/animal, IV-SCT vs. IBM-SCT, P = 1.90 × 10−10). In the late phase (5 days) after SCT, there were also significantly more donor cells in the lung after IV-SCT than after IBM-SCT or allogeneic-SCT (508.5 ± 66.1 vs. 160.1 ± 61.9 × 106 photons/s/animal, IV-SCT vs. IBM-SCT, P = 0.001), suggesting that the allogeneic reaction induces sustained donor cell infiltration in the lung during the late phase. These results demonstrated that IBM-SCT is capable of reducing injected donor cells in the lung; IBM-SCT decreases donor cell infiltration. IBM-SCT therefore represents a promising transplantation strategy for reducing pulmonary complications, by suppressing the first step in the pathophysiology of chronic GVHD. |
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language | English |
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spelling | doaj.art-5edcfc2734bf4df2b3b2ef8278cd17b22022-12-22T03:46:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01179Prevention of non-infectious pulmonary complications after intra-bone marrow stem cell transplantation in miceYoshiko Yamasuji-MaedaHisakazu NishimoriKeisuke SeikeAkira YamamotoHideaki FujiwaraTaiga KuroiKyosuke SaekiHaruko FujinagaSachiyo OkamotoKen-ichi MatsuokaNobuharu FujiiTakehiro TanakaMasahiro FujiiKatsumi MominokiTakuro KanekuraYoshinobu MaedaNon-infectious pulmonary complications including idiopathic pneumonia syndrome (IPS) and bronchiolitis obliterans syndrome (BOS), which are clinical and diagnostic manifestations of lung chronic graft-versus-host disease (GVHD), cause significant mortality after allogeneic stem cell transplantation (SCT). Increasing evidence suggests that alloantigen reactions in lung tissue play a central role in the pathogenesis of IPS and BOS; however, the mechanism is not fully understood. Several clinical and experimental studies have reported that intra-bone marrow (IBM)-SCT provides high rates of engraftment and is associated with a low incidence of acute GVHD. In the present study, allogeneic SCT was conducted in mouse models of IPS and BOS, to compare intravenous (IV)-SCT with IBM-SCT. Allogeneic IBM-SCT improved the clinical and pathological outcomes of pulmonary complications compared to those of IV-SCT. The mechanisms underlying the reductions in pulmonary complications in IBM-SCT mice were explored. The infiltrating lung cells were mainly CD11b+ myeloid and CD3+ T cells, in the same proportions as in transplanted donor cells. In an in vivo bioluminescence imaging, a higher proportion of injected donor cells was detected in the lung during the early phase (1 h after IV-SCT) than after IBM-SCT (16.7 ± 1.1 vs. 3.1 ± 0.7 × 105 photons/s/animal, IV-SCT vs. IBM-SCT, P = 1.90 × 10−10). In the late phase (5 days) after SCT, there were also significantly more donor cells in the lung after IV-SCT than after IBM-SCT or allogeneic-SCT (508.5 ± 66.1 vs. 160.1 ± 61.9 × 106 photons/s/animal, IV-SCT vs. IBM-SCT, P = 0.001), suggesting that the allogeneic reaction induces sustained donor cell infiltration in the lung during the late phase. These results demonstrated that IBM-SCT is capable of reducing injected donor cells in the lung; IBM-SCT decreases donor cell infiltration. IBM-SCT therefore represents a promising transplantation strategy for reducing pulmonary complications, by suppressing the first step in the pathophysiology of chronic GVHD.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9462704/?tool=EBI |
spellingShingle | Yoshiko Yamasuji-Maeda Hisakazu Nishimori Keisuke Seike Akira Yamamoto Hideaki Fujiwara Taiga Kuroi Kyosuke Saeki Haruko Fujinaga Sachiyo Okamoto Ken-ichi Matsuoka Nobuharu Fujii Takehiro Tanaka Masahiro Fujii Katsumi Mominoki Takuro Kanekura Yoshinobu Maeda Prevention of non-infectious pulmonary complications after intra-bone marrow stem cell transplantation in mice PLoS ONE |
title | Prevention of non-infectious pulmonary complications after intra-bone marrow stem cell transplantation in mice |
title_full | Prevention of non-infectious pulmonary complications after intra-bone marrow stem cell transplantation in mice |
title_fullStr | Prevention of non-infectious pulmonary complications after intra-bone marrow stem cell transplantation in mice |
title_full_unstemmed | Prevention of non-infectious pulmonary complications after intra-bone marrow stem cell transplantation in mice |
title_short | Prevention of non-infectious pulmonary complications after intra-bone marrow stem cell transplantation in mice |
title_sort | prevention of non infectious pulmonary complications after intra bone marrow stem cell transplantation in mice |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9462704/?tool=EBI |
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