Abstract

The study was aimed to investigate the mechanism and administration timing of bone marrow-derived mesenchymal stem cells (BMSCs) in bleomycin (BLM)-induced pulmonary fibrosis mice. Thirty-six mice were divided into six groups: control group (saline), model group (intratracheal administration of BLM), day 1, day 3 and day 6 BMSCs treatment groups and hormone group (hydrocortisone after BLM treatment). BMSCs treatment groups received BMSCs at day 1, 3 or 6 following BLM treatment, respectively. Haematoxylin and eosin and Masson staining were conducted to measure lung injury and fibrosis, respectively. Matrix metalloproteinase (MMP9), tissue inhibitor of metalloproteinase-1 (TIMP-1), γ -interferon (INF- γ ) and transforming growth factor β 1 (TGF- β ) were detected in both lung tissue and serum. Histologically, the model group had pronounced lung injury, increased inflammatory cells and collagenous fibres and up-regulated MMP9, TIMP-1, INF- γ and TGF- β compared with control group. The histological appearance of lung inflammation and fibrosis and elevation of these parameters were inhibited in BMSCs treatment groups, among which, day 3 and day 6 treatment groups had less inflammatory cells and collagenous fibres than day 1 treatment group. BMSCs might suppress lung fibrosis and inflammation through down-regulating MMP9, TIMP-1, INF- γ and TGF- β . Delayed BMSCs treatment might exhibit a better therapeutic effect. Copyright © 2015 John Wiley & Sons, Ltd. Highlights are as follows: BMSCs repair lung injury induced by BLM. BMSCs attenuate pulmonary fibrosis induced by BLM. BMSCs transplantation down-regulates MMP9 and TIMP-1. BMSCs transplantation down-regulates INF- γ and TGF- β . Delayed transplantation timing of BMSCs might exhibit a better effect against BLM.