Intravenously delivered multilineage-differentiating stress-enduring cells dampen hyperoxia-induced lung injury in a rat model with features of bronchopulmonary dysplasia

Stem Cell Research & Therapy

卷:17

Research

Ryosuke Miura^1,2  Atsuto Onoda^1,3  Azusa Okamoto¹  Toshihiko Suzuki¹  Takahiro Kanzawa¹  Sakiko Suzuki¹  Kazuto Ueda¹  Shinobu Shimizu⁴  Yoshiyuki Takahashi²  Masahiro Hayakawa¹  Yoshiaki Sato^1,2 

[1] Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, 466-8560, Nagoya, Aichi, Japan

[2] Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, 1-1-1 Daigakudori, 756-0884, Sanyo-Onoda, Yamaguchi, Japan

[3] Department of Advanced Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, 466-8560, Nagoya, Aichi, Japan

[4] Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, 466-8560, Nagoya, Aichi, Japan

关键词: Muse cells;    BPD;    Mesenchymal stromal cell;    Hyperoxia-induced neonatal lung injury model;   

DOI  :  10.1186/s13287-026-05086-2

 received in 2025-10-16, accepted in 2026-05-28,  发布年份 2026

来源: Springer

【 摘 要 】

BackgroundNeonatal bronchopulmonary dysplasia (BPD) is a lung injury caused by various factors, including intrauterine inflammation, mechanical ventilation, and oxidative stress. BPD results in serious respiratory and neurological dysfunctions and mortality. Recently, some clinical trials have commenced using intravenous delivery of donor-derived multilineage-differentiating stress enduring (Muse) cells. In the present study, we aimed to investigate the therapeutic effects of human Muse cells in hyperoxia-induced neonatal lung injury in a rat model with features of bronchopulmonary dysplasia.MethodsRats were put into the incubator within 24 h from birth to expose to hyperoxia (83%) until postnatal day 15. Muse and non-Muse cells, obtained from the bone marrow-mesenchymal stromal cells (MSCs) as stage-specific embryonic antigen-3 (SSEA-3)+ and −, respectively, were administered slowly via the right external jugular vein or trachea (Muse cells only) on postnatal day 5. For the vehicle groups, only the acetic acid Ringer's solution was administered.ResultsRespiratory function, histological findings, and inflammatory parameters did not differ significantly between intravenous and intratracheal administration. In contrast, body weight gain and survival were worse following intratracheal administration. Intravenous administration of Muse cells resulted in superior amelioration of lung tissue injury, inflammation, and pulmonary hypertension compared with non-Muse cells. We also confirmed the engraftment of Muse cells in the lung tissues. Proteomic profiling identified hyperoxia-induced lung injury associated changes in the abundance of proteins annotated to cell adhesion and coagulation/fibrinolysis-related pathways, and Muse cell administration was associated with differential abundance of subsets of these proteins.ConclusionsOur findings suggest that intravenously transplanted Muse cells provide functional benefits in hyperoxia-induced lung injury in a rat model with features of bronchopulmonary dysplasia.

【 授权许可】

CC BY   
© The Author(s) 2026

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