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dc.contributor.authorBartaula-Brevik, Sushmaen_US
dc.contributor.authorPedersen, Torbjorn Østviken_US
dc.contributor.authorBlois, Anna Len_US
dc.contributor.authorPapadakou, Panagiotaen_US
dc.contributor.authorFinne-Wistrand, Annaen_US
dc.contributor.authorXue, Yingen_US
dc.contributor.authorBolstad, Anne Isineen_US
dc.contributor.authorMustafa, Kamal Babikeir Elnen_US
dc.description.abstractIntroduction Inflammation plays a crucial role in tissue regeneration, wound healing, and the success of tissue-engineered constructs. The aim of this study was to investigate the influence of human umbilical vein endothelial cells (ECs) on leukocyte transmigration when co-cultured with primary human bone marrow-derived multipotent stromal cells (MSCs). Methods MSCs with and without ECs were cultured in poly (L-lactide-co-1, 5-dioxepan-2-one) (poly (LLA-co-DXO)) scaffolds for 1 week in vitro in a bioreactor system, after which they were implanted subcutaneously in non-obese diabetic/severe combined immunodeficient mice. After 1 and 3 weeks, scaffolds were retrieved, and the mRNA expression of interleukin 1-beta (IL-1β), IL-6, IL-10, hypoxia-inducible factor 1-alpha (HIF-1α), HIF-1β, and mammalian target of rapamycin was examined by real-time reverse transcription-polymerase chain reaction. Furthermore, immunofluorescent staining was performed for IL-1β, IL-6, neutrophils, and CD11b. In addition, Western blotting was done for IL-1β and IL-6. Leukocyte transmigration genes and genes in Toll-like receptor pathways, expressed by MSCs cultured in vitro with or without ECs, were further investigated with a microarray dataset. Results In vitro, genes involved in leukocyte transmigration and Toll-like receptor pathways were clearly influenced by the addition of ECs. Platelet/endothelial cell adhesion molecule-1 (PECAM-1) and cadherin-5 (CDH5), both genes involved in leukocyte transmigration, were expressed significantly higher in the MSC/EC group. In vivo, the MSC/EC group showed higher mRNA expression of hypoxia-inducible factors HIF-1α and HIF-1β. The mRNA expression of anti-inflammatory cytokine IL-10 showed no significant difference, whereas the mRNA and protein expression of pro-inflammatory cytokines IL-1β and IL-6 were lower in the MSC/EC group. The quantitative analysis of immunofluorescent staining revealed a significant difference in the number of neutrophils migrating into constructs, with the highest density found in the MSC/EC group. The number of macrophages positive for IL-6 and CD11b was significantly reduced in the MSC/EC group. Conclusions The recruitment of leukocytes into tissue-engineered constructs with MSCs is strongly influenced by the addition of ECs via activation of leukocyte transmigration and Toll-like receptor pathways.en_US
dc.publisherBioMed Centraleng
dc.relation.ispartof<a href="" target="blank">Vascularization and Host Response in Bone Tissue Engineering</a>
dc.rightsAttribution CC BYeng
dc.titleLeukocyte transmigration into tissue-engineered constructs is influenced by endothelial cells through Toll-like receptor signalingen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2014 Bartaula-Brevik et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
dc.rights.holderSushma Bartaula-Brevik et al.; licensee BioMed Central Ltd.
dc.source.journalStem Cell Research & Therapy

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