title: Mesenchymal stem cells transmigrate over the endothelial barrier.
abstract: Mesenchymal stem cells (MSCs) seem to be a useful tool for cellular therapy in injured tissues, e.g. myocardial infarction or cardiomyopathies resulting in heart failure. For therapeutic approaches it is crucial that MSCs cross the endothelial barrier especially in intravascular or rather intracoronary application. Until today little is known about MSCs transmigrating across the endothelium. We performed co-culture experiments of MSCs on an endothelial monolayer to analyse direct interactions. An increasing flattened morphology of the MSCs was followed by a total integration into the monolayer after 2h. We repeated these experiments in isolated heart perfusions with gold-labelled MSCs. Using electron microscopy we detected MSCs exhibited direct cell-cell contacts. Tight junctions between the endothelial cells became abolished resulting in a distinct split between the cells. MSCs developed tight cell-cell contacts and became integrated into the endothelial wall of the capillary vessel. Finally, using confocal laser scanning microscopy, we assessed the ability of the MSCs to fully pass the endothelial barrier. Within the first 30 min, 30+/-8% of MSCs transmigrated, increasing to about half at 60 min (50+/-8%), whereas after 120 min the rate remained nearly unchanged (53+/-10%). This work demonstrates the capability of MSCs for transendothelial migration. Moreover we showed that the vast majority of MSCs migrated within 30 min, an important finding for the exposure times in clinical settings.
authors.affiliation: Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Carl-Diem-Weg 6, D-50933 Cologne, Germany. a.schmidt@dshs-koeln.de
authors.forename: Annette
authors.initials: A
authors.lastname: Schmidt
authors.forename: Dennis
authors.initials: D
authors.lastname: Ladage
authors.forename: Caroline
authors.initials: C
authors.lastname: Steingen
authors.forename: Klara
authors.initials: K
authors.lastname: Brixius
authors.forename: Timo
authors.initials: T
authors.lastname: Schinköthe
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Klinz
authors.forename: Robert H G
authors.initials: RH
authors.lastname: Schwinger
authors.forename: Uwe
authors.initials: U
authors.lastname: Mehlhorn
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000378:metabolism