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dc.contributor.authorRymo, Simin
dc.date.accessioned2011-05-26T14:40:48Z
dc.date.available2011-05-26T14:40:48Z
dc.date.issued2011-05-26
dc.identifier.isbn978-91-628-8285-3
dc.identifier.urihttp://hdl.handle.net/2077/25576
dc.description.abstractABSTRACT Angiogenesis, the process by which new vessels sprout from pre-existing vessels, is fundamental to development, tissue growth and repair. The main aim of this thesis was to investigate the role of microglia on angiogenesis. We adapted the rat ex vivo/in vitro aortic ring model to the mouse in a 3-D culture system. In paper I, we show that ablation of microglia in the retina leads to a poorly developed vascular network. The aortic ring model, supplied with microglia, demonstrated that microglia have a direct positive effect on angiogenic sprouting. The angiogenic effect was mediated by soluble factor/factors, and cell-cell contacts were not required. We also show that the microglia-derived angiogenic factor(s) is distinct from vascular endothelial growth factor-A. Moreover, the sprouting aortic ring induces oriented migration of microglia towards the aortic ring. In paper II, we analysed the microglia transcriptome. We found that microglia express known activators and inhibitors of angiogenesis that might have a role in retinal blood vessel development. The aortic ring system was also used as a complement to in vivo analyses to address the function of sphingosine-1- phosphate receptor 1 (S1P1) on angiogenesis (paper III). The results indicate that S1P1 is required within endothelial cells to counteract VEGFA- signalling and prevent endothelial hyper-sprouting. In paper IV, expression of green fluorescent protein in endothelial/hematopoietic cells using Tie2-Cre was used to mark transplanted bone marrow-derived cells. The study aimed to address if grafted bone marrow derived cells can differentiate into pancreatic β-cells in mice. The major part of the thesis concerns the establishment and use of the mouse aortic ring as a model for angiogenesis. Importantly, application of the system enabled us to identify a direct positive effect of microglia on angiogenesis and to test putative modifiers. This could be further pursued by microarray analyses. The presented work might therefore provide a platform for the identification of molecules that regulate angiogenesis. Key words: microglia, angiogenesis, aortic ring. ISBN: 978-91-628-8285-3sv
dc.language.isoengsv
dc.relation.haspartI. Rymo SF, Gerhardt H, Wolfhagen Sand F, Lang R, Uv A, Betsholtz C. (2011). A two-way communication between microglial cells and angiogenic sprouts regulates angiogenesis in aortic ring cultures.PLoS One. 2011 Jan 10;6(1):e15846.::PMID::21264342sv
dc.relation.haspartII. Simin F. Rymo, Zulfeghar A. Syed, Anne Uv and Christer Betsholtz. A transcriptional profiling approach to identify microglia-derived factors that stimulate angiogenesis in aortic ring cultures. Manuscriptsv
dc.relation.haspartIII. Konstantin Gaengel, Kazuhiro Hagikura, Colin Niaudet, Lars Muhl, Staffan Nyström, Simin F. Rymo, Bàrbara Laviňa Siemsen, Jennifer Hofmann, Lwaki Ebarasi, Long Long Chen, Karin Strittmatter, Guillem Genove, Pernilla Roswall, Peter Lönneberg, Per Uhlen, Anne Uv, Arindam Majumdar, Richard L. Proia and Christer Betsholtz. S1P1 is a critical regulator of angiogenesis. Manuscriptsv
dc.relation.haspartIV.Rosengren AH, Taneera J, Rymo S, Renström E. (2009). Bone marrow transplantation stimulates pancreatic β-cell replication after tissue damage.Islets. 2009 Jul-Aug;1(1):10-8.::PMID::21084844sv
dc.subjectmicrogliasv
dc.subjectangiogenesissv
dc.subjectaortic ringsv
dc.titleOn the stimulatory effect of microglial cells on angiogenesissv
dc.typetexteng
dc.type.svepDoctoral thesiseng
dc.gup.mailsimin.rymo@medkem.gu.sesv
dc.type.degreeDoctor of Philosophy (Medicine)sv
dc.gup.originUniversity of Gothenburg. Sahlgrenska Academysv
dc.gup.departmentInstitute of Biomedicine. Department of Medical Biochemistry and Cell Biologysv
dc.gup.defenceplaceTid: 2011-06-16 kl 13:00, Plats: Medicinarberget - Arvid Carlsson, Medicinaregatan 3sv
dc.gup.defencedate2011-06-16
dc.gup.dissdb-fakultetSA


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