Therapeutic effect of human umbilical cord mesenchymal stem cells modified by angiotensin-converting enzyme 2 gene on bleomycin-induced lung fibrosis injury

Min,Fang; Gao,Fengying; Li,Qian; Liu,Zhenwei

doi:10.3892/mmr.2014.3025

Therapeutic effect of human umbilical cord mesenchymal stem cells modified by angiotensin-converting enzyme 2 gene on bleomycin-induced lung fibrosis injury

Authors:
- Fang Min
- Fengying Gao
- Qian Li
- Zhenwei Liu
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Affiliations: Department of Obstetrics, First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, P.R. China, Department of Respiratory Medicine, Shanghai Jiangong Hospital, Shanghai 200083, P.R. China, Department of Pediatrics, First People's Hospital of Kunshan, Affiliated to Jiangsu University, Kunshan 215300, P.R. China, Department of Respiratory Medicine, First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, P.R. China
Published online on: December 1, 2014 https://doi.org/10.3892/mmr.2014.3025
Pages: 2387-2396
Copyright: © Min et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The aim of the present study was to evaluate the therapeutic effects of human umbilical cord mesenchymal stem cells (uMSCs) in the presence of angiotensin‑converting enzyme 2 gene (ACE2; ACE2‑uMSCs) on bleomycin (BLM)‑induced lung injury and pulmonary fibrosis in mice. A total of 100 male C57BL/6 mice were divided at random into five groups (n=20) as follows: Control group, BLM group, ACE2 group, uMSC group and ACE2‑uMSC group. At 7, 14 and 28 days post‑treatment, the following parameters were evaluated in lung tissue: Oxidation indexes [malondialedehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and oxidized glutathione (GSSG)]; fibrosis factors [tumor necrosis factor (TNF)‑α, interferon (IFN)‑γ and transforming growth factor (TGF)‑β]; inflammatory cytokines [Interleukin (IL)‑1, IL‑2, IL‑6 and IL‑10]; ACE2 gene expression; hydroxyproline and collagen type 1 messenger RNA (mRNA) concentration; as well as matrix metalloproteinase (MMPs; 2 and 9) and tissue inhibitor of metalloproteinase (TIMP)1‑4 expression. ACE2‑uMSC injection following bleomycin pretreatment significantly alleviated lung injury in mice. In addition, treatment with ACE2‑uMSCs demonstrated a stronger therapeutic effect than ACE2‑ or uMSC treatment alone, indicated by decreased expression of MDA, GSSG, TNF‑α, IFN‑γ, TGF‑β, IL‑1, IL‑2, IL‑6, collagen type 1 mRNA, MMPs and TIMPs as well as hydroxyproline concentration, and upregulation of SOD, GSH and ACE2 and IL‑10. In conclusion, the results of the present study demonstrated that ACE2 and uMSCs had a synergistic therapeutic effect on bleomycin‑induced acute lung injury.

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