Published online Jul 26, 2022. doi: 10.4252/wjsc.v14.i7.556
Peer-review started: March 30, 2022
First decision: April 25, 2022
Revised: May 4, 2022
Accepted: June 20, 2022
Article in press: June 20, 2022
Published online: July 26, 2022
Processing time: 117 Days and 20.6 Hours
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.
To investigate whether hUC-MSC intratracheal administration could attenuate hyperoxia-induced lung, heart, and kidney injuries and the underlying regulatory mechanisms.
Neonatal rats were exposed to hyperoxia (80% O2), 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.
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
iT hUC-MSCs administration ameliorates hyperoxia-induced lung, heart, and kidney injuries by activating HO-1 expression and JAK/STAT signaling. The therapeutic benefits of local iT and iP administration are equivalent.
Core Tip: In the present study, we used a newborn rat model of postnatal hyperoxia exposure to simulate clinical bronchopulmonary dysplasia (BPD) and the associated heart and kidney injuries in preterm infants. Improved lung, heart, and kidney development, as well as reduced inflammatory and oxidative responses, were observed with human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) administration. We demonstrated that hUC-MSCs ameliorate hyperoxia-induced systemic organ injuries by activating heme oxygenase-1 expression and JAK/STAT pathway. Overall, our study shows that intratracheal administration is a more attractive route of MSCs administration in preterm infants for the prevention and treatment of BPD and hyperoxia-induced systemic damage.