Ryosuke Miura, Atsuto Onoda, Azusa Okamoto, Toshihiko Suzuki, Takahiro Kanzawa, Sakiko Suzuki, Kazuto Ueda, Shinobu Shimizu, Yoshiyuki Takahashi, Masahiro Hayakawa, Yoshiaki Sato
Nagoya University Hospital and Nagoya University Graduate School of Medicine. Sanyo-Onoda City University.
Japan
Stem Cell Research and Therapy
Stem Cell Res Ther 2026; 17:
DOI: 10.1186/s13287-026-05086-2
Abstract
Background: Neonatal 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.
Methods: Rats 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.
Results: Respiratory 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.
Conclusions: Our findings suggest that intravenously transplanted Muse cells provide functional benefits in hyperoxia-induced lung injury in a rat model with features of bronchopulmonary dysplasia.
Category
Class III. Pulmonary Hypertension Associated with Lung Disease
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Animal Models of Pulmonary Vascular Disease and Therapy
Medical Therapy. Efficacy or Lack of Efficacy
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes