Enhanced secretion of hepatocyte growth factor in human umbilical cord mesenchymal stem cells ameliorates pulmonary fibrosis induced by bleomycin in rats

Huanjie Chen; Yulong Luo; Yiping Zhu; Yongshun Ye; Difei Chen; Xinyu Song; Zhulin Xiao; Ming Liu; Shiyue Li

doi:10.3389/fphar.2022.1070736

Enhanced secretion of hepatocyte growth factor in human umbilical cord mesenchymal stem cells ameliorates pulmonary fibrosis induced by bleomycin in rats

Front Pharmacol. 2023 Jan 6:13:1070736. doi: 10.3389/fphar.2022.1070736. eCollection 2022.

Authors

Huanjie Chen¹, Yulong Luo², Yiping Zhu¹, Yongshun Ye³, Difei Chen¹, Xinyu Song¹, Zhulin Xiao¹, Ming Liu¹, Shiyue Li¹

Affiliations

¹ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
² Innovation Centre for Advanced Interdisciplinary Medicine, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
³ Huizhou Municipal Central Hospital, Guangzhou, Guangdong, China.

Abstract

Umbilical cord mesenchymal stem cells (UCMSCs) are a reportedly promising choice in the treatment of irreversible pulmonary fibrosis and lethal interstitial lung disease with limited drug treatment options. In this study, we investigated the therapeutic efficacy of UCMSCs overexpressing hepatocyte growth factor (HGF), which is considered one of the main anti-fibrotic factors secreted by MSCs. Adenovirus vector carrying the HGF gene was transfected into UCMSCs to produce HGF-modified UCMSCs (HGF-UCMSCs). Transfection promoted the proliferation of UCMSCs and did not change the morphology, and differentiation ability, or biomarkers. Rats were injected with HGF-UCMSCs on days 7 and 11 after intratracheal administration of bleomycin (10 mg/kg). We performed an analysis of histopathology and lung function to evaluate the anti-fibrotic effect. The results showed that HGF-UCMSCs decreased the Ashcroft scores in hematoxylin and eosin-stained sections, the percentage positive area in Masson trichrome-stained sections, and the hydroxyproline level in lungs. Forced expiratory volume in the first 300 m/forced vital capacity was also improved by HGF-UCMSCs. To explore the possible therapeutic mechanism of HGF-UCMSCs, we detected inflammatory factors in the lungs and performed mRNA sequencing in UCMSCs and HGF-UCMSCs. The data indicated that inhibition of interleukin-17 in the lung may be related to the anti-fibrosis of HGF-UCMSCs, and overexpressed HGF probably played a primary role in the treatment. Collectively, our study findings suggested that the overexpression of HGF may improve the anti-fibrotic effect of UCMSCs through directly or indirectly interacting with interleukin-17-producing cells in fibrotic lungs.

Keywords: hepatocyte growth factor; interleukin-17; mesenchymal stem cells; pulmonary fibrosis; umbilical cord.

Grants and funding

This research was supported by Innovation team of respiratory diseases and regenerative medicine (2021KCXTD028), Zhongnanshan medical foundation of Guangdong Province (ZNSA-2020013), the Guangzhou Science and Technology Project (202102010358) and Basic Research Foundation of Guangzhou (202102020916).