Onderzoek is een belangrijk onderdeel van het fonds. Vanuit de historie richtte Tekke Huizinga samen met Professor Kolff de eerste bloedbank van het Academisch Ziekenhuis op. Huizinga en Kolff waren echte pioniers op hun werkgebied.
Deze pioniersgedachte ligt ook ten grondslag aan de doelstellingen van het Tekke Huizinga Fonds, een bijdrage leveren aan vernieuwende ideeën of een eerste verkennende uitwerking daarvan binnen de aangegeven werkgebieden hematologie, transfusiegeneeskunde of gelieerde onderzoeksgebieden.
Sinds 2004 zijn meer dan twintig onderzoeksprojecten gehonoreerd, die waren aangevraagd door onderzoekers van Sanquin, UMCG en MST (Medisch Spectrum Twente). De onderstaande onderzoeken geven een beeld van de onderzoeksgebieden die voor een bijdrage in aanmerking kwamen.
Development of microthrombi in kidney preservation and transplantation – the new kid on the block?
Ms. T. van den Berg, BSc
The occurrence of microthrombi can potentially lead to local perfusion disorders and subsequently to deterioration of kidney graft function. We hypothesize that microthrombi are more frequent than we might expect, due to known activation of haemostatic pathways in deceased donors, the ischemia/reperfusion injury that occurs during the transplant surgery and enhanced kidney function after thrombolytic therapy. The aim of this study is to investigate how often these microthrombi occur, which consequences they bear and whether type of preservation influences their development and hemostatic processes.
Neonatal anemia and red blood cell transfusions
Ms. W. Kalteren, BSc
This project addresses the benefits and risks of the RBC transfusion in neonatal anemia in preterm born infants. The lack of knowledge on the balance of potential benefits and risk of RBC transfusion for anemic preterm infants, have led to controversies about the optimal indication for RBC transfusion for this population. Therefore, the overall aim of this research project is to clarify controversial issues regarding neonatal anemia and RBC transfusion. First, we intend to assess the feasibility of using a lower than conventional transfusion Hb-threshold combined with the degree of oxygen saturation of the brain. Second, we intend to increase knowledge of the association between anemia and epo gene expression and on the direct biochemical and functional effects of RBC transfusion in preterm infants regarding organ oxygenation, clinical factors, intestinal hypoxic cell damage, oxidative stress, and neurodevelopment.
Effects of prohemostatic interventions on hemostatic status of patients with liver disease in a clinical setting
Mrs. F. von Meijenfeldt, BSc
Lipidomic and proteomic analysis of potentially transplantable lungs undergoing ex vivo lung perfusion (EVLP)
Dr. Ing. R. Hoffmann
3DA treatment as a possible enhancer of hematopoietic stem cell function.
Ms. S. Buisman, BSc
Hematopoietic stem cell transplantation is established as a treatment for a broad range of hematological diseases. However, suboptimal engraftment levels and low availability of hematopoietic stem cells (HSCs) limit the use. This highlights the importance of finding ways to maintain and expand the available HSCs and enhance their engraftment potential. In this project we test 3-DEAZAADENOSINE (3DA) as a candidate drug for preventing/blunting senescence. Preliminary in vitro data showed that 3DA treated cord blood CD34+ cells maintained more primitive. The Tekke Huizinga grant enabled us to further investigate whether in vitro 3DA treatment is able to enhance in vivo human HSC capacity.
Resuscitation of discarded donor human hearts on subnormothermic ex-situ machine perfusion with an acellular perfusate
Mr. V. van Suylen
Currently, there is no clinical practice of donation after circulatory death (DCD) heart transplantation in the Netherlands. In addition, certain donation after brain death (DBD) hearts are not transplanted due to the existing strict selection criteria. This study will develop a preservation technique for discarded human donor hearts. It will focus on the effect of subnormothermic acellular machine perfusion on the inflammatory and oxidative status, energy storage capacity, and restoration of function of donor hearts currently deemed unsuitable for transplantation. To study the effect of this preservation technique, we will evaluate these hearts using a normothermic ex-situ heart perfusion machine. The advantage of this machine is its ability to assess the function of the hearts as well as biochemical parameters.
Clinical validation of the analysis of Everolimus, Sirolimus, and Mycophenolate Mofetil in Dried Blood Spots
Prof.dr. D. Touw
Towards rational hemostatic management of critically ill patients with liver disease
Prof.dr. J.A. Lisman
Liver disease is associated with complex changes in the hemostatic system. Although routine indices of hemostasis such as the platelet count and prothrombin time suggest a bleeding tendency, these patients are in fact in hemostatic balance due to a simultaneous decline in pro- and anticoagulant drivers. Whether this rebalanced hemostatic state remains when patients with liver disease become critically ill is unknown and subject of this proposal. Knowledge on the hemostatic status of critically ill patients with liver disease is vital for a rational approach to hemostatic management.
Is poor stem cell mobilization related to the emergence of clonal haematopoiesis in the bone marrow compartment?
Ms. I. van Zeventer, BSc, BA
Some patients fail to mobilize sufficient numbers of CD34+ peripheral blood stem cells upon mobilization procedures for autologous hematopoietic cell transplantation. It is now known that clonal haematopoiesis might emerge during ageing and following chemotherapeutic treatment, implying a risk for development of myeloid neoplasms. We aim to study the presence of clonal haematopoiesis in poor mobilizers by a targeted sequencing approach and to relate the mutational profile to clinical outcomes and development of secondary haematological malignancies. Results from this study may contribute to improved and personalized treatment protocols.
Adult stem cells of the human thyroid gland; expansion and functionality
Prof.dr. R.P. Coppes
Insufficient levels of thyroid hormone due to cancer treatment related thyroidectomy may lead to fatigue, feeling cold, constipation, and weight increase; whereas high levels may lead to cardiovascular diseases or osteoporosis. In this project we developed a culture protocol for murine and human thyroid stem cell derived tissue resembling organoids. When xeno-transplanted into athyroid mice, these organoids form functional hormone producing thyroid follicles. This opens future therapeutic possibilities for tissue stem cell-based therapies for thyroid cancer patients suffering from hypothyroidism.
This project was a collaboration with Andries Groen, Prof. dr. John Plukker, Dr. Schelto Kruijff (all Surgical Oncology) and Prof. Thera Links (Endocrinology).
Dissecting the epigenetic events that contribute to hematopoietic stem cell expansion
Ms. K. Mattes
Leukemia stem cells play a crucial role in disease initiation and progression of acute myeloid leukemia (AML). We identified that altered expression of the transcriptional regulators CITED2 and PU.1 impacts the survival and maintenance of both normal- and leukemia stem cells. With support of “Tekke Huizingafonds” we investigated potential molecular mechanisms underlying this observation. Understanding the mechanisms that regulate stem cell self-renewal and survival can help to improve current protocols for hematopoietic stem cell transplantation or highlight opportunities for AML therapy.
Hibernation as key to unlock platelet cold storage
Mr. E.L. de Vrij
Long term cold storage of human platelets for transfusion is not yet possible due to detrimental effects of low temperature on platelets causing rapid clearance after transfusion. Studies on platelets in hibernating animals do not show these detrimental effects of temperature, despite cycling through extreme temperatures. In this project we assessed the effects of temperature on platelet function in mice mimicking ‘daily hibernation’ and by using intravital microscopy analysis. Studying hibernators and their protective mechanisms against cold may unlock platelet cold storage for non-hibernating mammals.
The hemostatic status of critically ill patients with liver disease
Prof.dr. J.A. Lisman
Towards ex vivo normothermic machine perfusion of human donor livers without the requirement for human blood products
Ms. A. Matton
Multipotent donor lung therapy with mesenchymal stem cells in an ex vivo lung perfusion model using lungs from brain dead donorrats
Dr. M.E. Erasmus – UMCG
Brain death and ischemia cause inflammatory and mitochondrial injury to donor lungs. In our project we stabilized the damaging process by giving stem cells during ex situ perfusion and ventilation of rat donor lungs pre-transplant. Multiple smaller doses were most efficient.
Understanding erythropoiesis from (expanded) hematopoietic stem cells through modulation of CITED2
Dr. H. Schepers – UMCG
With this proposal we will investigate the cellular and molecular mechanisms that the transcriptional regulator CITED2 uses in order to expand HSC numbers. We will furthermore gain a deeper understanding how CITED2 increases the overall erythroid output from these cells.
Organ preservation with hydrogensulfide in renal transplantation
Prof. dr. H. van Goor – UMCG
Hydrogen sulfide has protective properties during ischemia. It can hypometabolize cells and tissues comparable to cooling down. We currently uss this concept to protect transplant organs in the phases prior to transplantation.
Dissecting the architecture of the normal and leukemic ‘stem cell niche’
Drs. C.L.E. Hazenberg – UMCG
In this research proposal, we study the changes in the bone marrow microenvironment of patients after autologous stem cell transplantation. By understanding the changes in the cellular compartments and the molecular pathways involved, we aim to improve future transplantation strategies and post-transplantational care, in order to improve patients’ outcomes.
Efficacy of pro- and antihemostatic drugs in plasma from patients with liver disease
Prof. dr. J.A. Lisman – UMCG
This study has shown tremendous alterations in the anticoagulant effect of widely used drugs in plasma from patients with cirrhosis as compared to individuals with intact liver function (PLoS One. 2014 Feb 4;9(2):e88390). Our data may have important implications for dosing anticoagulant drugs in patients with cirrhosis.
Pilotstudie ‘normotherme machinepreservatie van humane donorlevers’
Dr. S. op den Dries – UMCG
A prospective cohort piloty study for use of cryolijm-sq in patients with severe COPD
Dr. M. Tiekstra-Dijkstra – UMCG
Detection of ischemia/reperfusion injury in human tissue: Anti-aggregatory and anti-inflammatory ectoenzymes in vascular endothelium.
Dr. F. Spaans – UMCG
Bone marrow derived endothelial progenitor cell transplantation to ameliorate radiation-induced vascular remodelling in the lung
Prof. dr. R.P. Coppes – UMCG
Exploiting possibilities to improve the long-term engrafment of the hematopoietic stem cell compartment following autologous stem cell transplantation
Dr. E. Vellenga- UMCG
Transfusion policy in patients with complex changes of hemostatis – a rebalanced hemostatic status in patients with acute liver failure
Prof. Dr. J.A. Lisman – UMCG
Transfusion as supportive care, study for improvement of quality of life
Dr. J. Slomp – MST, Enschede
Will reinfusion of autologous stem cell products, independent of the composition of the transplant, directly in the bone marrow compartment improve steady state hematopoiesis post-transplantation?
Prof. Dr. E. Vellenga – UMCG
The PLATO study disfunctionerende plaatjes bij lever transplantaties en preserverende werking van aprotinine
Prof. Dr. R.J. Porte – UMCG
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