title: Excess Integrins Cause Lung Entrapment of Mesenchymal Stem Cells.
abstract: Mesenchymal stem cells (MSCs) are largely entrapped in the lungs after intravenous delivery. The underlying mechanisms have been poorly understood. Flow cytometry and Western blot analysis showed that the expression levels of many integrins such as β1, α5, and αVβ3 in MSCs increased markedly upon cultured expansion in 2D monolayers, whose ligands fibronectin and vitronectin were detected on the surface of vascular endothelial cells in the lungs by immunostaining and flow cytometry. Blockade of integrin β1, integrin α5, or integrins αVβ3 with functional blocking antibodies significantly decreased the amount of MSCs entrapped in the lungs following intravenous infusion as determined by real-time PCR and histological analysis; meanwhile, corresponding increases in the levels of circulating MSCs in the blood and MSCs homed to the ischemic myocardium and inflamed ear were found. Intriguingly, a short period of 3D spheroid culture of MSCs, which had been expanded for several passages in monolayers, substantially reduced the expression levels of many integrins and the number of MSCs entrapped in the lungs. Our results indicate that the excess expression and activation of integrins is a significant cause of lung entrapment of MSCs.
authors.affiliation: School of Life Sciences, Tsinghua University, People's Republic of China.|The Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: The Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
authors.affiliation: School of Life Sciences, Tsinghua University, People's Republic of China.|The Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, People's Republic of China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Ge
authors.affiliation: Peking University Shenzhen Hospital, Shenzhen Key Laboratory of Gynecological Diagnostic Technology Research, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.affiliation: School of Life Sciences, Tsinghua University, People's Republic of China.|The Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Cai
authors.affiliation: The Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, People's Republic of China.
authors.forename: Ruiyun
authors.initials: R
authors.lastname: Tian
authors.affiliation: State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University, People's Republic of China.
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Beijing, People's Republic of China.
authors.forename: Robert Ch
authors.initials: RCh
authors.lastname: Zhao
authors.affiliation: The Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, People's Republic of China.
authors.forename: Yaojiong
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D016023:Integrins / Q000096:biosynthesis*; D008168:Lung / Q000166:cytology* / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy
chemical_list: D016023:Integrins
keywords: Homing; Integrins; Lung entrapment; Mesenchymal stem cells; Vascular obstructions