Human Endometrial Regenerative Cells Attenuate Bleomycin-Induced Pulmonary Fibrosis in Mice

Endometrial regenerative cells (ERCs) have been recently evaluated as an attractive novel type of stem cell therapy. Previous studies have demonstrated that most ERCs accumulated in the lung after injection and are successfully used to treat diseases such as cardiac fibrosis. However, relevant studi...

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Main Authors: Yiming Zhao, Xu Lan, Yong Wang, Xiaoxi Xu, Shanzheng Lu, Xiang Li, Baoren Zhang, Ganggang Shi, Xiangying Gu, Caigan Du, Hao Wang
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2018/3475137
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author Yiming Zhao
Xu Lan
Yong Wang
Xiaoxi Xu
Shanzheng Lu
Xiang Li
Baoren Zhang
Ganggang Shi
Xiangying Gu
Caigan Du
Hao Wang
author_facet Yiming Zhao
Xu Lan
Yong Wang
Xiaoxi Xu
Shanzheng Lu
Xiang Li
Baoren Zhang
Ganggang Shi
Xiangying Gu
Caigan Du
Hao Wang
author_sort Yiming Zhao
collection DOAJ
description Endometrial regenerative cells (ERCs) have been recently evaluated as an attractive novel type of stem cell therapy. Previous studies have demonstrated that most ERCs accumulated in the lung after injection and are successfully used to treat diseases such as cardiac fibrosis. However, relevant studies of ERCs in idiopathic pulmonary fibrosis (IPF) have not been reported. The present study was designed to examine the effects of ERCs on bleomycin-induced pulmonary fibrosis. All IPF models in C57BL/6 mice were induced by administrating 5 mg/kg bleomycin in PBS intratracheally. ERCs were isolated from healthy female menstrual blood and were injected (1 million/mouse, i.v.) 24 hours after induction. Wet/dry weight ratio assay, hydroxyproline content, pathological and immunohistological changes, MDA content, T-SOD activity, cytokine profiles, and RT-qPCR analysis were assessed 2 weeks after disease induction. The results showed that ERC treatment significantly decreased the wet/dry ratio and reduced collagen deposition. Histological analyses, Masson staining, and hydroxyproline content analysis indicated that ERCs could reduce collagen fiber production. Immunohistochemical staining revealed lower expression of TGF-β after ERC treatment. Furthermore, mice treated with ERCs had lower levels of IL-1β and TNF-α, but a higher level of IL-10 in both the lung and serum. Gene expression analysis demonstrated that ERCs potently suppressed the proapoptotic gene Bax, while increasing the antiapoptotic gene Bcl-2 and antifibrosis genes HGF and MMP-9. Our results indicate that human ERCs protected the lung from pulmonary fibrosis in mice through immunosuppressive and antifibrosis effects. Moreover, these findings formed a foundation for the further use of ERCs in clinical treatment.
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spelling doaj-art-a539143d073f4d46bc068efdbbb3dc952025-08-20T02:23:05ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/34751373475137Human Endometrial Regenerative Cells Attenuate Bleomycin-Induced Pulmonary Fibrosis in MiceYiming Zhao0Xu Lan1Yong Wang2Xiaoxi Xu3Shanzheng Lu4Xiang Li5Baoren Zhang6Ganggang Shi7Xiangying Gu8Caigan Du9Hao Wang10Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of General Surgery, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Ultrasonography, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Anorectal Surgery, People’s Hospital of Hunan Province, First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, ChinaDepartment of General Surgery, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of General Surgery, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Colorectal Surgery, The Second Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Urologic Sciences, The University of British Columbia, Vancouver, BC, CanadaDepartment of General Surgery, Tianjin Medical University General Hospital, Tianjin, ChinaEndometrial regenerative cells (ERCs) have been recently evaluated as an attractive novel type of stem cell therapy. Previous studies have demonstrated that most ERCs accumulated in the lung after injection and are successfully used to treat diseases such as cardiac fibrosis. However, relevant studies of ERCs in idiopathic pulmonary fibrosis (IPF) have not been reported. The present study was designed to examine the effects of ERCs on bleomycin-induced pulmonary fibrosis. All IPF models in C57BL/6 mice were induced by administrating 5 mg/kg bleomycin in PBS intratracheally. ERCs were isolated from healthy female menstrual blood and were injected (1 million/mouse, i.v.) 24 hours after induction. Wet/dry weight ratio assay, hydroxyproline content, pathological and immunohistological changes, MDA content, T-SOD activity, cytokine profiles, and RT-qPCR analysis were assessed 2 weeks after disease induction. The results showed that ERC treatment significantly decreased the wet/dry ratio and reduced collagen deposition. Histological analyses, Masson staining, and hydroxyproline content analysis indicated that ERCs could reduce collagen fiber production. Immunohistochemical staining revealed lower expression of TGF-β after ERC treatment. Furthermore, mice treated with ERCs had lower levels of IL-1β and TNF-α, but a higher level of IL-10 in both the lung and serum. Gene expression analysis demonstrated that ERCs potently suppressed the proapoptotic gene Bax, while increasing the antiapoptotic gene Bcl-2 and antifibrosis genes HGF and MMP-9. Our results indicate that human ERCs protected the lung from pulmonary fibrosis in mice through immunosuppressive and antifibrosis effects. Moreover, these findings formed a foundation for the further use of ERCs in clinical treatment.http://dx.doi.org/10.1155/2018/3475137
spellingShingle Yiming Zhao
Xu Lan
Yong Wang
Xiaoxi Xu
Shanzheng Lu
Xiang Li
Baoren Zhang
Ganggang Shi
Xiangying Gu
Caigan Du
Hao Wang
Human Endometrial Regenerative Cells Attenuate Bleomycin-Induced Pulmonary Fibrosis in Mice
Stem Cells International
title Human Endometrial Regenerative Cells Attenuate Bleomycin-Induced Pulmonary Fibrosis in Mice
title_full Human Endometrial Regenerative Cells Attenuate Bleomycin-Induced Pulmonary Fibrosis in Mice
title_fullStr Human Endometrial Regenerative Cells Attenuate Bleomycin-Induced Pulmonary Fibrosis in Mice
title_full_unstemmed Human Endometrial Regenerative Cells Attenuate Bleomycin-Induced Pulmonary Fibrosis in Mice
title_short Human Endometrial Regenerative Cells Attenuate Bleomycin-Induced Pulmonary Fibrosis in Mice
title_sort human endometrial regenerative cells attenuate bleomycin induced pulmonary fibrosis in mice
url http://dx.doi.org/10.1155/2018/3475137
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