BACKGROUND
Bronchopulmonary dysplasia (BPD) is not merely a chronic lung disease, but a systemic condition with multiple organs implications predominantly associated with hyperoxia exposure. Despite advances in current management strategies, limited progress has been made in reducing the BPD-related systemic damage. Meanwhile, although the protective effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) or their exosomes on hyperoxia-induced lung injury have been explored by many researchers, the underlying mechanism has not been addressed in detail, and few studies have focused on the therapeutic effect on systemic multiple organ injury.
AIM
To investigate whether hUC-MSC intratracheal administration could attenuate hyperoxia-induced lung, heart, and kidney injuries and the underlying regulatory mechanisms.
METHODS
Neonatal rats were exposed to hyperoxia (80% O
2
), treated with hUC-MSCs intratracheal (iT) or intraperitoneal (iP) on postnatal day 7, and harvested on postnatal day 21. The tissue sections of the lung, heart, and kidney were analyzed morphometrically. Protein contents of the bronchoalveolar lavage fluid (BALF), myeloperoxidase (MPO) expression, and malondialdehyde (MDA) levels were examined. Pulmonary inflammatory cytokines were measured
via
enzyme-linked immunosorbent assay. A comparative transcriptomic analysis of differentially expressed genes (DEGs) in lung tissue was conducted
via
RNA-sequencing. Subsequently, we performed reverse transcription-quantitative polymerase chain reaction and western blot analysis to explore the expression of target mRNA and proteins related to inflammatory and oxidative responses.
RESULTS
iT hUC-MSCs administration improved pulmonary alveolarization and angiogenesis (
P
< 0.01,
P
< 0.01,
P
< 0.001, and
P
< 0.05 for mean linear intercept, septal counts, vascular medial thickness index, and microvessel density respectively). Meanwhile, treatment with hUC-MSCs iT ame liorated right ventricular hypertrophy (for Fulton’s index,
P
< 0.01), and relieved reduced nephrogenic zone width (
P
< 0.01) and glomerular diameter (
P
< 0.001) in kidneys. Among the beneficial effects, a reduction of BALF protein, MPO, and MDA was observed in hUC-MSCs groups (
P
< 0.01,
P
< 0.001, and
P
< 0.05 respectively). Increased pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-1β, and IL-6 expression observed in the hyperoxia group were significantly attenuated by hUC-MSCs administration (
P
< 0.01,
P
< 0.001, and
P
< 0.05 re...