We study repair of diseased (transplant) organs by use of cellular therapies on a fundamental and more translational level. Our research includes the use of cells for immunomodulatory therapies, cells for repair of injured tissues, and the generation of organoids that can be used to study organ disease and regeneration.
Mesenchymal stromal cell research
Our research group has studied mesenchymal stromal cells (MSC) as a potential therapy for kidney transplantation since 2006. Research has initially focused on the mechanisms of action of the immunomodulatory effect of MSC, thereby contributing to the identification of key molecules in the interaction between MSC and various types of immune cells. In addition we have developed an interest in the fate of MSC after intravenous infusion and upon arterial administration to transplant organs on machine perfusion. More recently, research has expanded to MSC-derived extracellular vesicles, and in particular to vesicles generated of reconstructed membranes of MSC. We are exploring the effect of these membranes on endothelial cell survival and function under inflammatory and hypoxic conditions.
We perform our research in collaboration with colleagues at other research institutes and medical centers in amongst others Leiden, Groningen, Regensburg, Aarhus, Oxford, Birmingham and Takeda-TiGenix company. The research has led to close to 100 publications, 6 PhD theses, and multiple Master theses.
Kidney organoid research
Since 2015 our research group works on the generation of kidney organoids from induced pluripotent stem cells (iPSC) as a model for kidney regeneration research. During a 3-4 week protocol iPSC differentiate and organize in organoids with clear tubular and glomerular structures, endothelial cells and stromal cells, resembling 1st trimester kidney. As the differentiation of iPSC to kidney organoids is highly complex, our group is monitoring this process in detail by studying metabolic and gene expression changes in the organoids and by using single cell sequencing techniques. One of the important functions of the kidney is its endocrine function and we are therefore examining and modifying the ability of organoids to produce kidney hormones such as renin and EPO. Finally, kidney organoids are an excellent model to study kidney disease or to test novel drugs. For this research we are collaborating with several Departments within the Erasmus MC and internationally with the German Cancer Research Center in Heidelberg.
The endothelium plays a central role in organ degeneration and regeneration. The endothelium is sensitive to immune and hypoxic injury, but a good functioning endothelium is crucial for enabling regenerative processes in organs to occur. Our group is studying endothelial reconstruction through decellularisation and recellularisation of hepatic and renal veins. Furthermore, we are studying the role of endogenous circulating endothelial cells in transplant kidney repair short and long after transplantation. Finally, we are exploring methodology to vascularize kidney organoids in vitro using an organ-on-chip device build by the Delft biotech startup BI/OND.
For more information on tissue repair and cell therapy applications within the Rotterdam Transplantation laboratory please contact:
Martin Hoogduijn, PhD