title: Intravenous and intratracheal mesenchymal stromal cell injection in a mouse model of pulmonary emphysema.
abstract: The aim of this study was to characterize the evolution of lung function and -structure in elastase-induced emphysema in adult mice and the effect of mesenchymal stromal cell (MSC) administration on these parameters. Adult mice were treated with intratracheal (4.8 units/100 g bodyweight) elastase to induce emphysema. MSCs were administered intratracheally or intravenously, before or after elastase injection. Lung function measurements, histological and morphometric analysis of lung tissue were performed at 3 weeks, 5 and 10 months after elastase and at 19, 20 and 21 days following MSC administration. Elastase-treated mice showed increased dynamic compliance and total lung capacity, and reduced tissue-specific elastance and forced expiratory flows at 3 weeks after elastase, which persisted during 10 months follow-up. Histology showed heterogeneous alveolar destruction which also persisted during long-term follow-up. Jugular vein injection of MSCs before elastase inhibited deterioration of lung function but had no effects on histology. Intratracheal MSC treatment did not modify lung function or histology. In conclusion, elastase-treated mice displayed persistent characteristics of pulmonary emphysema. Jugular vein injection of MSCs prior to elastase reduced deterioration of lung function. Intratracheal MSC treatment had no effect on lung function or histology.
authors.affiliation: 1Department of Physiology and Experimental Medicine, Hospital for Sick Children, Toronto, Canada.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Tibboel
authors.forename: Richard
authors.initials: R
authors.lastname: Keijzer
authors.forename: Irwin
authors.initials: I
authors.lastname: Reiss
authors.forename: Johan C
authors.initials: JC
authors.lastname: de Jongste
authors.forename: Martin
authors.initials: M
authors.lastname: Post
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005540:Forced Expiratory Flow Rates; D007275:Injections, Intravenous; D007601:Jugular Veins; D008176:Lung Volume Measurements; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D010196:Pancreatic Elastase; D011650:Pulmonary Alveoli / Q000473:pathology; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D014132:Trachea
chemical_list: D010196:Pancreatic Elastase
keywords: MSC; elastase; histology; jugular vein; morphometry