Human umbilical cord-derived mesenchymal stem cells protect from hyperoxic lung injury by ameliorating aberrant elastin remodeling in the lung of O2-exposed newborn rat

Chen Hou; Danyi Peng; Li Gao; Daiyin Tian; Jihong Dai; Zhengxiu Luo; Enmei Liu; Hong Chen; Lin Zou; Zhou Fu

doi:10.1016/j.bbrc.2017.12.055

Human umbilical cord-derived mesenchymal stem cells protect from hyperoxic lung injury by ameliorating aberrant elastin remodeling in the lung of O₂-exposed newborn rat

Biochem Biophys Res Commun. 2018 Jan 8;495(2):1972-1979. doi: 10.1016/j.bbrc.2017.12.055. Epub 2017 Dec 12.

Authors

Chen Hou¹, Danyi Peng², Li Gao³, Daiyin Tian⁴, Jihong Dai⁴, Zhengxiu Luo⁴, Enmei Liu⁴, Hong Chen⁵, Lin Zou⁶, Zhou Fu⁷

Affiliations

¹ Pediatrics Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China; Chongqing Key Laboratory of Pediatrics, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, China.
² Pediatrics Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China; Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing 400014, China; Chongqing Key Laboratory of Pediatrics, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, China.
³ Pediatrics Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China; Department of Otorhinolaryngology, Children's Hospital of Chongqing Medical University, Chongqing 400014, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, China.
⁴ Pediatrics Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China; Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
⁵ Pediatrics Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China; Chongqing Key Laboratory of Pediatrics, China; Department of Pediatrics, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
⁶ Pediatrics Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China; Center for Clinical Molecular Medicine, Children's Hospital of Chongqing Medical University, Chongqing 400014, China; Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing 400014, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, China. Electronic address: zoulin74@126.com.
⁷ Pediatrics Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China; Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing 400014, China; Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing 400014, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, China. Electronic address: fu_zhou79@126.com.

PMID: 29242152
DOI: 10.1016/j.bbrc.2017.12.055

Abstract

The incidence and mortality rates of bronchopulmonary dysplasia (BPD) remain very high. Therefore, novel therapies are imminently needed to improve the outcome of this disease. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) show promising therapeutic effects on oxygen-induced model of BPD. In our experiment, UC-MSCs were intratracheally delivered into the newborn rats exposed to hyperoxia, a well-established BPD model. This study demonstrated that UC-MSCs reduce elastin expression stimulated by 90% O₂ in human lung fibroblasts-a (HLF-a), and inhibit HLF-a transdifferentiation into myofibroblasts. In addition, the therapeutic effects of UC-MSCs in neonatal rats with BPD, UC-MSCs could inhibit lung elastase activity and reduce aberrant elastin expression and deposition in the lung of BPD rats. Overall, this study suggested that UC-MSCs could ameliorate aberrant elastin expression in the lung of hyperoxia-induced BPD model which may be associated with suppressing increased TGFβ1 activation.

Keywords: Bronchopulmonary dysplasia; Elastin; TGF-β1; UC-MSCs; α-SMA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Bronchopulmonary Dysplasia / immunology*
Bronchopulmonary Dysplasia / pathology*
Cells, Cultured
Cord Blood Stem Cell Transplantation / methods*
Elastin / metabolism*
Humans
Hyperbaric Oxygenation
Hyperoxia / metabolism
Hyperoxia / pathology
Hyperoxia / prevention & control
Lung / immunology*
Lung / pathology*
Lung Injury / immunology
Lung Injury / pathology
Lung Injury / prevention & control
Mesenchymal Stem Cell Transplantation / methods*
Rats
Rats, Sprague-Dawley
Treatment Outcome

Substances

Elastin