Antonius J. Rabelink - Biography#

Ton Rabelink is a clinician-scientist who has been active in the cell and developmental biology of the kidney and endothelium since 1986. He became professor of nephrology and vascular medicine by special appointment of the Dutch Kidney Foundation at the age of 37. and have since created a wide network of collaborators with the common aim to bring new solutions for patients with kidney disease. The basis to do so lays in basic science of vascular biology and kidney regeneration over the years resulting in >700 publications; H index = 73; I100 = 50; Citations >22,000; and 2 granted patents. I am the figurehead of Regenerative Medicine in the Netherlands and leading the kidney “moonshot” of the European public-private partnership RegMed XB. I was recently interviewed (https://www.nature.com/articles/d41586-020-00671-8) as an expert in this area by Nature News Features on "How artificial kidneys and miniaturized dialysis could save millions of lives". I have also established NECSTGEN, the Leiden regenerative medicine center, which will house a GMP-facility for research and development of Advanced Therapy Medicinal Products, accessible at low cost to academia and SMEs. As cofounder of the Netherlands Epidemiology of Obesity (NEO) study (which included 6500 individuals), I am responsible for research in the genetic and metabolic cause of kidney disease which resulted in co-authorships on a Nature Genetics and two Nature Communication papers in 2019. My current team consists of 5 postdocs, 4 PhD-students, and 3 research technicians who work together to bridge my two passions, endothelial cell biology and regenerative medicine.

Endothelial cell biology

Over the last 10 years the focus of my group has been on vascular and endothelial cell biology. Areas of interest include the intracellular signalling of endothelial cells (in particular eNOS function and uncoupling) and the role of endothelial progenitors in endothelial regeneration and repair (Patent US6544994B2). My group has actively pursued the translation of insights in vascular biology to the field of kidney disease. Exemplified by the research on tissue engineering of a vascular access graft for which a patent was granted (NL2013016, spun out as VACIS BV). In addition, my lab made significant contributions to the role of endothelial progenitors in endothelial regeneration and repair. We were the first to describe how diabetes interferes with vascular healing by progenitor cells. Currently, we focus on the coupling of cell metabolism with the surface glyco-landscape of endothelial cells, which is critical to all endothelial signalling. We discovered how the glycobiosynthesis in the kidney is conditional to glomerular integrity and revealed how cell metabolism couples to maturation of hiPSC-derived endothelial cells.

Kidney regeneration and bioengineering

My second and more recent passion is kidney regeneration. This is approached from different angles 1) using the body’s intrinsic capacity to regenerate in immunologically favourable situations through the use of mesenchymal stromal cells (MSC). In this context I coordinated an FP7 EU consortium (STELLAR, 6M€). And 2) using human induced pluripotent stem cell (hiPSC)-derived kidney organoids for which we established the protocol. For the MSC work we were the first to apply this in solid organ transplantation and have successfully concluded two phase I trials, showing safety and feasibility of both autologous and allogeneic MSC in kidney transplantation. A phase II trial just finished accrual in which MSC are tested for their ability to reduce fibrosis and prevent kidney graft rejection under withdrawal of tacrolimus, an immunosuppressive drug. In addition, we have led investigator-initiated outcome studies in CKD. This shows our translational capacity in cell therapy and regenerative medicine field as well as the dedication to bring our research to patients. I was awarded honorary fellowships to the European Renal Association and German Society of Nephrology for this. In our work on hiPSC-derived kidney organoids, we combine our insights on endothelial cell biology with our experience in stem cell biology. We have shown feasibility to reendothelialize a human kidney scaffold with iPSC-derived endothelial cells and investigate the possibility to provide auxiliary kidney tissue to take over part of the kidney function using hPSC-derived organoids. We were the first to show that kidney organoids mature upon transplantation, become vascularized and show active filtration.

Websites containing more information:

https://www.universiteitleiden.nl/en/staffmembers/a.j.-rabelink#tab-1
http://www.einthovenlaboratory.com/ton-rabelink
https://rg.lumc.nl/en
http://www.stellarproject.eu
http://eu-msc2.blogspot.com