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...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9462704/?tool=EBI
_version_ 1811211285253062656
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.
first_indexed 2024-04-12T05:10:18Z
format Article
id doaj.art-5edcfc2734bf4df2b3b2ef8278cd17b2
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-04-12T05:10:18Z
publishDate 2022-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
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
work_keys_str_mv AT yoshikoyamasujimaeda preventionofnoninfectiouspulmonarycomplicationsafterintrabonemarrowstemcelltransplantationinmice
AT hisakazunishimori preventionofnoninfectiouspulmonarycomplicationsafterintrabonemarrowstemcelltransplantationinmice
AT keisukeseike preventionofnoninfectiouspulmonarycomplicationsafterintrabonemarrowstemcelltransplantationinmice
AT akirayamamoto preventionofnoninfectiouspulmonarycomplicationsafterintrabonemarrowstemcelltransplantationinmice
AT hideakifujiwara preventionofnoninfectiouspulmonarycomplicationsafterintrabonemarrowstemcelltransplantationinmice
AT taigakuroi preventionofnoninfectiouspulmonarycomplicationsafterintrabonemarrowstemcelltransplantationinmice
AT kyosukesaeki preventionofnoninfectiouspulmonarycomplicationsafterintrabonemarrowstemcelltransplantationinmice
AT harukofujinaga preventionofnoninfectiouspulmonarycomplicationsafterintrabonemarrowstemcelltransplantationinmice
AT sachiyookamoto preventionofnoninfectiouspulmonarycomplicationsafterintrabonemarrowstemcelltransplantationinmice
AT kenichimatsuoka preventionofnoninfectiouspulmonarycomplicationsafterintrabonemarrowstemcelltransplantationinmice
AT nobuharufujii preventionofnoninfectiouspulmonarycomplicationsafterintrabonemarrowstemcelltransplantationinmice
AT takehirotanaka preventionofnoninfectiouspulmonarycomplicationsafterintrabonemarrowstemcelltransplantationinmice
AT masahirofujii preventionofnoninfectiouspulmonarycomplicationsafterintrabonemarrowstemcelltransplantationinmice
AT katsumimominoki preventionofnoninfectiouspulmonarycomplicationsafterintrabonemarrowstemcelltransplantationinmice
AT takurokanekura preventionofnoninfectiouspulmonarycomplicationsafterintrabonemarrowstemcelltransplantationinmice
AT yoshinobumaeda preventionofnoninfectiouspulmonarycomplicationsafterintrabonemarrowstemcelltransplantationinmice