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

摘要

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.