title: Paracrine factors from mesenchymal stem cells attenuate epithelial injury and lung fibrosis.
abstract: Paracrine factors are currently considered to be the major mechanism through which mesenchymal stem cells (MSCs) exert their actions. The aim of this study was to investigate the protective effects of conditioned medium (CM) from bone marrow mesenchymal stem cells (MSC) on bleomycin (BLM)‑induced lung injury and fibrosis, both in vitro and in vivo. A549 human non‑small cell lung cancer epithelial cells were cultured in serum‑free medium, or MSC‑CM, both with or without BLM. The protective effects of MSC‑CM was determined by MTT assay to assess cell viability and Annexin V‑PE to assess apoptosis. Rats were intratracheally injected with MSC‑CM, saline, or conditioned medium from fibroblasts on day 0 and day 3 after intratracheal administration of BLM, and were sacrificed on day 28. Lung injury and fibrosis were assessed by histological assessment, Ashcroft score, and hydroxyproline assay; lung cell apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling assay. In comparison to the control group (0.17±0.01), 8 and 16% MSC‑CM had a significant stimulatory effect on A549 cellular proliferation (0.24±0.03 and 0.24±0.04, respectively, P<0.01). A549 cells cultured with MSC‑CM were protected from BLM‑induced apoptosis, 23.43±3.76% vs. 38.06±4.32%; (P<0.05). In the BLM‑challenged rats, MSC‑CM was shown to protect against lung fibrosis in terms of lung inflammation, fibrotic scores, collagen deposition, and cell apoptosis. This data suggests that MSCs are capable of protecting against lung injury and fibrosis both in vitro and in vivo through a paracrine anti‑inflammatory mechanism. MSC‑CM may provide a novel approach for the treatment of lung fibrosis.
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Department of Respiratory and Critical Care Medicine, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Key Laboratory of Molecular Development Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100190, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.affiliation: Key Laboratory of Molecular Development Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100190, P.R. China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Department of Respiratory and Critical Care Medicine, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Lifen
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Department of Respiratory and Critical Care Medicine, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Xu
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Department of Respiratory and Critical Care Medicine, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Pathology Medicine, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Mulan
authors.initials: M
authors.lastname: Jin
authors.affiliation: Key Laboratory of Molecular Development Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100190, P.R. China.
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Department of Respiratory and Critical Care Medicine, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Huaping
authors.initials: H
authors.lastname: Dai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin / Q000009:adverse effects; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004195:Disease Models, Animal; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D019899:Paracrine Communication; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D051381:Rats
chemical_list: D017077:Culture Media, Conditioned; D001761:Bleomycin