Intravenously delivered Multilineage-differentiating stress enduring cells dampen in experimental bronchopulmonary dysplasia rat model

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 a BPD rat model. 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 Regarding the administration route, intravenous administration was superior to intratracheal administration in terms of improving survival, weight gain, and respiratory function. When administered intravenously, the Muse cells showed superior outcomes in ameliorating respiratory function impairment, lung inflammation, pulmonary hypertension, and anti-inflammatory effects, compared to the non-Muse cells. We also confirmed the engraftment of Muse cells in the lung tissues. A proteomic analysis also showed that Muse cells might have additional effects on the abnormalities in cell adhesion and the blood coagulation/fibrinolytic system caused by BPD. Conclusions Our findings suggested that intravenously transplanted Muse cells provided functional benefits in our experimental BPD rat model.