The Landsteiner Foundation for Blood Transfusion Research (LSBR) supports clinical and experimental scientific research in the field of blood, blood-forming tissue, blood products, and blood (related) diseases, provided that the research bears a relationship to the field of transfusion or transplantation of blood cells.

Submission of Pre-Applications for Scientific Research Projects is closed.

In 2017 the LSBR granted:

• 1707 (Fellowship) R. Bierings – Institute: Sanquin – Plasma Proteins
Von Willebrand factor release from Weibel-Palade bodies: pulling the strings in vascular disease
The endothelium is a thin layer of endothelial cells and forms the inner lining of our blood vessel, which separates blood from the underlying tissue. The vessel wall is equipped with a number of self-healing properties that prevent infection and excessive blood loss upon vascular injury. Following trauma the endothelium rapidly releases a vascular first aid kit, the Weibel-Palade body (WPB), which helps to recruit leukocytes to sites of inflammation. From the WPB it also releases long strings of Von Willebrand factor (VWF), which are adhesive for platelets and which are crucial for the formation of a platelet plug. Failure to release (sufficient amounts of) VWF leads to bleeding, such as in Von Willebrand disease (VWD). In this project I will use endothelial cells from patients to study the formation and release of WPBs in order to better understand the mechanisms that prevent excessive bleeding in healthy individuals and how abnormalities in these mechanisms result in disease.

• 1703 – G. de Haan- Institute: UMCG – Ageing Biology and Stem Cells
Dissecting the role of Neogenin; a novel receptor required for hematopoietic stem cell proliferation and engraftment
All blood cells in the human body are produced by a small population of stem cells that reside in the bone marrow. These stem cells can be transplanted in patients in which blood cell formation has stopped, mostly after high dose chemotherapy. These stem cells can also be used to genetically correct inherited blood diseases. For many of these clinical applications it would be highly beneficial if blood-forming stem cells could be cultured and expanded outside of the body, prior to their transplant. However, so far it has been very difficult to achieve this. In our lab we have now discovered a new receptor molecule that is present on blood-forming stem cells and that plays a key role in stem cell growth in culture and their transplantability. In this project we wish to explore the role of this molecule and try to improve stem cell functioning and increase their numbers in culture by activating this novel receptor.

• 1719 – C. Voermans/S.S. Zeerleder – Institute: Sanquin – Hematopoiesis/AMC – Hematology
The role of heme oxygenase-1 in the development of graft versus host disease
Allogeneic hematopoietic stem cell transplantation (HSCT) is widely applied to cure hematological malignancies. The main limitation of allogeneic HSCT however, is the development of graft-versus-host disease (GvHD), which is associated with high morbidity and mortality. Systemic inflammation in patients after allogeneic HSCT seems to increase the risk on activation of donor cells and thereby enhances the risk of GvHD. Heme-oxygenase (HO-1) is a stress-inducible enzyme that plays a pivotal role in anti-inflammation and immunosuppression. The current project will contribute to unravel the role of HO-1 in the development and severity of GvHD. Within this project, we will use already operational preclinical models and investigate longitudinal samples of HSCT patients. The results of this project will offer novel insights in the development of GvHD and can lead to new intervention strategies for patients to diminish the incidence and severity of GvHD.

• 1702 – J.C.M. Meijers – Institute: Sanquin – Plasma Proteins
Modifying factor XI to promote hemostasis: a novel therapeutic approach to control bleeding?
Bleeding is an important complication in patients and can be life-threatening. Therefore, a good strategy to stop blood loss by improving the patient’s coagulation system is essential. A number of alternatives are currently available, but these are either not specific or not sufficiently powerful to stop all bleedings. In this proposal, we aim to modify one of the coagulation factors in such a way that it will become a specific, but also safe enhancer of the coagulation pathway. This approach may be useful to treat bleeding after trauma or surgery, but also help patients with disturbed coagulation because they lack one or more of the coagulation factors.

• 1711 – J.W.M. Heemskerk – Institute: UM – Biochemistry
Platelet subsets and priming: functional determinants in haemostasis and vascular protection
Platelets circulating in the blood are highly diverse, as it is now becoming clear. Distinct subsets of platelets can be identified with differences in size, properties and composition. How this heterogeneity links to the main functions of platelets relevant for transfusion science is however fully unclear. In this project, we will start to unravel this, focussing on the roles of platelets in stopping a bleeding at an injured vessel wall (haemostasis), and by filling in the gaps between discontinuous endothelial cells (vascular protection). We will also determine platelet subsets are modulated by local endothelial mediators and stable hormones, by a process called priming. The work plan includes: (A) separation of platelets into various fractions by a range of techniques, with functional analysis of these fractions; (B) testing of the fractions with consistent low/high function profiles in whole-blood models of haemostasis and vascular protection; (C) Confirmative in vivo evaluation.

• 1721 – G. Vidarsson – Institute: Sanquin – Experimental Immunohematology
The Ig-glycan code: a third level of memory controlling effector function of immunoglobulins in health and disease
Blood transfusion is a common practice for various indications (e.g. anemia, sickle cell disease, surgery or acute blood loss due to injury). In some cases, antibodies are formed, needing extensive blood matching. Similarly, antibodies can be formed in pregnancy causing life-threatening diseases in the fetus and the newborn, e.g. antibodies to Rhesus. We have recently discovered a unique mechanism resulting in altered antibodies with higher destructive potency due to altered sugars in the antibodies. Our preliminary findings suggest these responses to have evolved against certain viral infection, which we accidentally trigger by mismatched transfusion or pregnancy. Here we plan to investigate this further and identify the exact mechanisms behind it. This proposed research project aims to unravel these mechanisms for even safer blood transfusions by allowing us to identify patients at risk, but also providing a sound basis for improving vaccines against difficult targets such as HIV.