title: Therapeutic effects of adipose-derived stem cells pretreated with pioglitazone in an emphysema mouse model.
abstract: There is no therapy currently available that influences the natural history of disease progression in patients with chronic obstructive pulmonary disease (COPD). Although stem cell therapy is considered a potential therapeutic option in COPD, there are no clinical trials proving definitive therapeutic effects in patients with COPD. Recently, it was reported that pioglitazone might potentiate the therapeutic effects of stem cells in patients with heart or liver disease. To test the capacity of pioglitazone pretreatment of stem cells for emphysema repair, we evaluated the therapeutic effects of pioglitazone-pretreated human adipose-derived mesenchymal stem cells (ASCs) on elastase-induced or cigarette smoke-induced emphysema in mice. We also investigated the mechanisms of action of pioglitazone-pretreated ASCs. Pioglitazone-pretreated ASCs had a more potent therapeutic effect than non-pretreated ASCs in the repair of both elastase-induced and smoke-induced emphysema models (mean linear intercept, 78.1±2.5 μm vs 83.2±2.6 μm in elastase models and 75.6±1.4 μm vs 80.5±3.2 μm in smoke models, P<0.05). Furthermore, we showed that pioglitazone-pretreated ASCs increased vascular endothelial growth factor (VEGF) production both in vitro and in mouse lungs in the smoke-induced emphysema model. Pioglitazone-pretreated ASCs may have more potent therapeutic effects than non-pretreated ASCs in emphysema mouse models.
authors.affiliation: Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Korea.
authors.forename: Yoonki
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Asan Institute for Life Sciences, Department of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: You-Sun
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Korea.
authors.forename: Seok-Ho
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Yeon-Mok
authors.initials: YM
authors.lastname: Oh
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008810:Mice, Inbred C57BL; D010196:Pancreatic Elastase; D000077205:Pioglitazone; D011656:Pulmonary Emphysema / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D012906:Smoke / Q000009:adverse effects; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D012906:Smoke; D045162:Thiazolidinediones; D010196:Pancreatic Elastase; D000077205:Pioglitazone