Kidney organoid and scaffold research

In our research group we combine two complementary research themes to generate insight in the development of alternative, innovative strategies for tissue engineering: 1) kidney scaffolds and 2) stem cells. Our approach ultimately strives to overcome the shortage of human donor organs by using the patient’s own cells for kidney bioengineering.

In the past couple of years complex organs such as liver, kidney and lung have been used for the generation of biocompatible scaffolds. We developed this concept further to use the kidneys as a source of expandable human kidney tissue and focus on the techniques for recellularization of this complex organ. We investigate whether the scaffold itself remains instructive and supportive for recellularization and therefore aim to characterize the biochemical components of the human kidney scaffold and the role of the extracellular matrix in morphology, migration, proliferation, differentiation and cell survival. In specially designed organ culture chambers we re-recellularize the vasculature with kidney derived endothelial cells and endothelial cells and kidney cells derived from induced pluripotent stem cells (hiPSCs).

hiPSCs are derived in the laboratory by reprogramming somatic cells and can self-replicate indefinitely and differentiate to all cells of the human body, including kidney cells. We make use of a unique culture protocol to differentiate these cells to intermediate mesoderm that subsequently further specializes to form kidney organoids that contain complete nephrons. These nephrons include all cap mesenchyme derived elements such as podocytes, tubular segments, stromal cells and endothelium, as well as the ureteric bud-derived components such as the collecting duct. Furthermore, scanning and transmission electron microscopy analysis shows the presence of foot processes in the glomerular structures and characteristic microvilli and mitochondria in the tubular structures that have an open lumen. We currently focus on maturation and vascularization of the kidney organoids.