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Leukocyte transmigr...
Leukocyte transmigration into tissue-engineered constructs is influenced by endothelial cells through Toll-like receptor signaling
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Bartaula-Brevik, Sushma (författare)
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Pedersen, Torbjorn O. (författare)
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Blois, Anna L. (författare)
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Papadakou, Panagiota (författare)
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- Finne-Wistrand, Anna (författare)
- KTH,Polymerteknologi
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Xue, Ying (författare)
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Bolstad, Anne Isine (författare)
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Mustafa, Kamal (författare)
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(creator_code:org_t)
- 2014-12-20
- 2014
- Engelska.
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Ingår i: Stem Cell Research & Therapy. - : Springer Science and Business Media LLC. - 1757-6512. ; 5, s. 143-
- Relaterad länk:
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https://stemcellres....
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- Introduction: 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-1 beta), IL-6, IL-10, hypoxia-inducible factor 1-alpha (HIF-1 alpha), HIF-1 beta, and mammalian target of rapamycin was examined by real-time reverse transcription-polymerase chain reaction. Furthermore, immunofluorescent staining was performed for IL-1 beta, IL-6, neutrophils, and CD11b. In addition, Western blotting was done for IL-1 beta 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-1 alpha and HIF-1 beta. The mRNA expression of anti-inflammatory cytokine IL-10 showed no significant difference, whereas the mRNA and protein expression of pro-inflammatory cytokines IL-1 beta 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Nyckelord
- Mesenchymal Stem-Cells
- Marrow Stromal Cells
- Gene-Expression Profiles
- Bone Regeneration
- Nitric-Oxide
- In-Vitro
- Inflammation
- Scaffolds
- Differentiation
- Biomaterials
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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