Intratracheal administration of umbilical cord-derived mesenchymal stem cells attenuates hyperoxia-induced multi-organ injury via heme oxygenase-1 and JAK/STAT pathways  

作　　者：Na Dong Pan-Pan Zhou Dong Li Hua-Su Zhu Ling-Hong Liu Hui-Xian Ma Qing Shi Xiu-Li Ju 

机构地区：[1]Department of Pediatrics,Qilu Hospital,Cheeloo College of Medicine,Shandong University,Jinan 250012,Shandong Province,China [2]Department of Pediatrics,Qilu Hospital of Shandong University,Jinan 250012,Shandong Province,China [3]Stem Cell and Regenerative Medicine Research Center,Qilu Hospital of Shandong University,Jinan 250012,Shandong Province,China

出　　处：《World Journal of Stem Cells》2022年第7期556-576,共21页世界干细胞杂志（英文版）（电子版）

基　　金：Supported by Rongxiang Regenerative Medicine Foundation of Shandong University, No. 2019SDRX-18;Clinical Practical New Technology Development Found of Qilu Hospital of Shandong University, No. KYC 2019-0057;Clinical Research Center of Shandong University, No. 2020SDUCRCA010;Natural Science Foundation of Shandong Province, No. ZR2020MH063

摘　　要：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),myeloper oxidase(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 ameliorated right ventricular hypertrophy(for Fulton’s index,P<0.01),and relieved reduced nephrogenic zone width(P<0.01)and glomerular diamet

关 键 词：Mesenchymal stem cell HYPEROXIA Multiple organ injury Bronchopulmonary dysplasia Heme oxygenase-1 JAK/STAT pathway 

分 类 号：R722.1[医药卫生—儿科]