The Therapeutic Effects of Optimal Dose of Mesenchymal Stem Cells in a Murine Model of an Elastase Induced-Emphysema.

BACKGROUND: Chronic obstructive pulmonary disease is characterized by emphysema, chronic bronchitis, and small airway remodeling. The alveolar destruction associated with emphysema cannot be repaired by current clinical practices. Stem cell therapy has been successfully used in animal models of cigarette smoke- and elastase-induced emphysema. However, the optimal dose of mesenchymal stem cells (MSCs) for the most effective therapy has not yet been determined. It is vital to determine the optimal dose of MSCs for clinical application in emphysema cases. METHODS: In the present study, we evaluated the therapeutic effects of various doses of MSCs on elastase-induced emphysema in mice. When 3 different doses of MSCs were intravenously injected into mice treated with elastase, only 5×10(4) MSCs showed a significant effect on the emphysematous mouse lung. We also identified action mechanisms of MSCs based on apoptosis, lung regeneration, and protease/antiprotease imbalance. RESULTS: The MSCs were not related with caspase-3/7 dependent apoptosis. But activity of matrix metalloproteinase 9 increased by emphysematous lung was decreased by intravenously injected MSCs. Vascular endothelial growth factor were also increased in lung from MSC injected mice, as compared to un-injected mice. CONCLUSION: This is the first study on the optimal dose of MSCs as a therapeutic candidate. This data may provide important basic data for determining dosage in clinical application of MSCs in emphysema patients.