Basic Study
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World J Stem Cells. Jul 26, 2022; 14(7): 556-576
Published online Jul 26, 2022. doi: 10.4252/wjsc.v14.i7.556
Intratracheal administration of umbilical cord-derived mesenchymal stem cells attenuates hyperoxia-induced multi-organ injury via heme oxygenase-1 and JAK/STAT pathways
Na Dong, Pan-Pan Zhou, Dong Li, Hua-Su Zhu, Ling-Hong Liu, Hui-Xian Ma, Qing Shi, Xiu-Li Ju
Na Dong, Hua-Su Zhu, Department of Pediatrics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
Pan-Pan Zhou, Xiu-Li Ju, Department of Pediatrics, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Dong Li, Ling-Hong Liu, Hui-Xian Ma, Qing Shi, Xiu-Li Ju, Stem Cell and Regenerative Medicine Research Center, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Author contributions: Dong N and Zhou PP completed the experiment and analyzed the results statistically; Ju XL and Li D proposed the design and conception of the experiment; Zhu HS and Liu LH assisted with the collection of tissue and blood samples from animals and gene expression experiments; Ma HX and Shi Q supervised the animal protocols and integrated the materials; Dong N wrote the first manuscript of the study; Ju XL and Li D revised the manuscript critically; all authors have read and approved the final manuscript.
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; and Natural Science Foundation of Shandong Province, No. ZR2020MH063.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee on Scientific Research of Qilu Hospital of Shandong University, No. KYLL-2019(KS)-086.
Institutional animal care and use committee statement: All animal procedures and protocols complied with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Ethics Committee on Animal Experiments of Shandong University Qilu Hospital, Jinan, China, No. DWLL-2021-035.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiu-Li Ju, PhD, Chief Doctor, Department of Pediatrics, Qilu Hospital of Shandong University, No. 107 Wenhua West Road, Jinan 250012, Shandong Province, China. jxlqlyy@163.com
Received: March 30, 2022
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
Core Tip

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.