SciLifeLab The Svedberg seminar series 2013-11-18
Department of Medical Cell Biology, Uppsala University, Sweden
“The role of leukocytes in angiogenesis and tissue repair”
Blood vessel growth, angiogenesis, is a tightly regulated process involving not only endothelial cells, but also several other cell types present at the site of angiogenesis. Leukocytes are known to accumulate at sites of hypoxia and were recently identified as key players in the process of vessel neo-formation. The dynamics of leukocyte involvement in angiogenesis, as well as their exact pro-angiogenic actions are still largely unknown. To address this, we developed a model that allows for in vivo visualization and tracking of leukocytes during angiogenesis, where isolated pancreatic islets are transplanted to the cremaster muscle of genetically identical recipient mice. In this model, leukocytes, endothelial cells and blood flow are studied in parallel at the site of hypoxia using high-speed in vivo confocal microscopy. Using this approach, we have identified muscle as a promising site for islet transplantation to diabetic recipients, as well as a distinct population of circulating proangiogenic neutrophils that is recruited to hypoxia where they have a crucial role in angiogenesis. The underlying mechanisms for the recruitment of these proangiogenic neutrophils as well as their action at the target site are now further investigated. We apply inference-based visualization following cell tracking to visualize behaviour and interactions of involved cells. In addition, induced expression of certain leukocyte-recruiting chemokines at sites of tissue injury is evaluated in respect to restoration of functional tissue perfusion using the ischemic hind limb model. Thus, different in vivo imaging models are used to gain important information of the identities and actions of different leukocyte populations during angiogenesis.
Host: Johan Elf