Exp Mol Med.  2016 Oct;48(10):e266. 10.1038/emm.2016.93.

Therapeutic effects of adipose-derived stem cells pretreated with pioglitazone in an emphysema mouse model

Affiliations
  • 1Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Korea.
  • 2Asan Institute for Life Sciences, Department of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Seoul, Korea.
  • 3Department of Pulmonary and Critical Care Medicine, Asan Medical Center, Seoul, Korea. ymoh55@amc.seoul.kr

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"‰Î¼m vs 83.2±2.6"‰Î¼m in elastase models and 75.6±1.4"‰Î¼m vs 80.5±3.2"‰Î¼m 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.


MeSH Terms

Animals
Disease Progression
Emphysema*
Heart
Humans
In Vitro Techniques
Liver Diseases
Lung
Mesenchymal Stromal Cells
Mice*
Natural History
Pancreatic Elastase
Pulmonary Disease, Chronic Obstructive
Smoke
Stem Cells*
Therapeutic Uses*
Tobacco Products
Vascular Endothelial Growth Factor A
Pancreatic Elastase
Smoke
Therapeutic Uses
Vascular Endothelial Growth Factor A
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