Prevention of non-infectious pulmonary complications after intra-bone marrow stem cell transplantation in mice

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

Research output: Contribution to journalArticlepeer-review


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 intrabone 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.

Original languageEnglish
Article numbere0273749
JournalPloS one
Issue number9 September
Publication statusPublished - Sept 2022

ASJC Scopus subject areas

  • General


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