Forskningsprosjekter Vaskulær Biologi
EU project (human liver sinusoidal endothelial cells – LSECs): HeMiBio (www.hemibio.eu)
Our research group is one of 11 partners of a 7-nation EU project funded under the 7th Framework Programme: HEPATIC MICROFLUIDIC BIOREACTOR (HeMiBio), with a 5-year duration starting 2011-01-01. The goal of HeMiBio is to develop a hepatic microfluidic bioreactor from human inducible pluripotent stem cells (iPSC)-derived hepatocytes, hepatic sinusoidal endothelial cells and stellate cells, suitable for inclusion in a repeated dose toxicity testing strategy of pharmaceuticals/cosmetic ingredients. The central objective of HeMiBio is to engineer the cellular components incorporated in the bioreactor, and, by gene editing, to allow non-invasive monitoring of the cellular state (differentiation and damage) to provide an alternative to using animals in pharma and cosmetics motivated hepatotoxicity studies.
Our research group was chosen as a HeMiBio partner due to our high standing international reputation as LSEC experts. The specific task assigned to VBRG in Tromsø is to screen candidate LSECs generated from iPSC to determine if they i) carry out the signature uptake functions of native LSECs, and ii) express the signature membrane proteins, in particular endocytosis receptors, of same cells.
As a consequence of our partnership in HeMiBio we are about to establish a method for isolation of LSECs and other cells from human liver. Until now we and practically all other groups working with LSECs have used animal models to study these cells. As a consequence of our partnership in HeMiBio we have now a unique possibility of widening up our research portfolio to include human liver, which will strengthen our position as a translational biomedical research group.
Bone marrow project (mouse and human bone marrow sinusoidal endothelial cells – BMSECs)
Bone marrow stem cells are responsible for the production of all red (oxygen transporting)/ white (immune) cells and platelets (clotting). They reside within a microenvironment termed the “stem cell niche”. Interfacing between the blood and the niche are vessels lined with sinusoidal endothelial cells (SEC). These cells, like their cousins in the liver (LSEC), have an immense endocytic capacity for soluble waste molecules, probably removing the refuse from the massive cell production in the bone marrow. The aims of our studies at VBRG are:
1. to exploit this endocytic capacity as a functional marker to isolate bone-marrow SEC (BMSEC), and assess their potential to improve bone-marrow transplantations via revascularisation and restoration of the niche post ablation;
2. to investigate the relationship between LSEC and BMSEC, and determine if BMSEC are the bone-marrow progenitors of LSEC;
3. determine the role of BMSEC in homing of stem cells and malignant cells that cause bone-marrow cancer.
This work is funded by Northern Norway Regional Health Authority (Helse Nord RHF) and Tromsø Research Foundation, and is a collaboration among Professor Inger Marie Skeibrok Dahl at the University Hospital of North Norway, Tromsø, VBRG at the University of Tromsø, Professor Staffan Johansson, Uppsala University, and Professor Susie Nilsson, CSIRO Materials Science and Engineering, Clayton, Australia.
The Scavenger Endothelial Cell – a novel important element in the innate immune system
Specialized scavenger endothelial cells (SEC), including the endothelial cells of the mammalian liver sinusoid, have recently been found by us and others to play an important role in homeostasis and immunity, where they constitute a non-leukocyte system for high capacity elimination of many unwanted self- and non-self macromolecules. The major goal of the project is to characterize SEC in developing and ageing, including both invertebrate and vertebrate models. The project further aims to investigate the interaction of SEC with immune modulators and immune cells, and determine the role of SEC in virus elimination and pathogenesis. This will establish the role of SEC in homeostasis and healthy ageing, and aims to provide a foundation for the development of SEC based therapies to treat diseases associated with pathological deposits associated with old age.
This work is funded by Tromsø Research Foundation and is in collaboration with Prof. David LeCouteur, University of Sidney; Prof. emer. Clive Crossley, University of Tasmania, Australia; Prof. Robert McCuskey, University of Arizona, USA; Dr. Cristina Rinaldo, University Hospital of North Norway, Tromsø; Prof. Hans Hirsch – University of Basel, Switzerland; Prof. Staffan Johansson –Uppsala University, Sweden; and Professor Sergei Goerdt – University of Heidelberg, Germany.
Scientific advisers to pharma industry and non-commercial units engaged in the development of large molecular drugs, frequently referred to as biopharmaceuticals.
Basing its activities and service portfolio on the long standing and unique knowledge and expertise provided by research carried out at VBRG, the newly established company D’Liver will offer delivery analysis and development packages to customers who are in the process of developing biopharmaceuticals (large molecule drugs such as for instance various enzymes, coagulation factors, DNA, siRNA). D’Liver is a commercial unit separate from the university, and will rely on the possibility of purchasing advises and collaborative projects from VBRG.