Senescent cell accumulation & Research-based undergraduate education

Abstract

In part 1 of this thesis, the accelerated aging process of damaged kidney cells (“cellular senescence) in Chronic Kidney Disease (CKD), and targets for intervention are explored. Senescent kidney cells contribute to renal failure through scarring of kidney tissue and loss of function. We show that renal senescent cells accumulate in scarred kidney tissue in two groups of CKD patients: kidney transplant recipients and childhood cancer survivors (as complication of their treatment). From the reviewed literature and these observations, we conclude that CKD patients may benefit from elimination of renal senescent cells by so called “senotherapeutics”. We identified two important factors that contribute to senescent cell accumulation in the context of renal injury. First, aging magnifies senescent cell numbers after renal injury, suggesting that especially elderly may benefit from senotherapeutic therapy. Next, the molecule CCN2 plays an important role in renal senescent cell accumulation after kidney transplantation. Our findings suggest that an inhibitor of CCN2 is a promising senotherapeutic CKD treatment. For identifying other factors or targets for senescence in the kidney, we developed a screening tool using kidney cells that are in a state that resembles senescence. In part 2 of this thesis, implementation of a new translational medicine educational concept in which students conduct research into a real medically relevant problem, in biomedical bachelor education is evaluated. We show that bachelor students successfully design studies, acquire funding and execute laboratory-studies. Further, they develop important academic skills. This provides a new insight into the involvement of bachelor students in biomedical research.