Guiding the immune response in in situ tissue engineered vascular access grafts
Arteriovenous (AV)-grafts ensure vascular access for hemodialysis treatment in end-stage renal disease (ESRD) patients. However, the currently used AV-grafts easily occlude due to thrombosis and intragraft neo-intimal hyperplasia. In situ tissue engineering is a promising new approach to reduce this vascular access dysfunction. The InSiTeVx project aims to develop an off-the-shelf, synthetic, biodegradable, AV-graft that will develop in vivo into a living, self-healing vascular access graft.
Upon implantation of the graft (Figure A), host immune cells infiltrate the fibrous graft. Especially macrophages are important in attracting (myo)fibroblasts (Figure B) to initiate tissue formation. The interplay between macrophages and (myo)fibroblasts leads to either healthy, functional tissue formation (Figure C) or adverse remodeling. Although the feasibility of vascular in situ tissue engineering has been proven, the endogenous remodeling processes are not well understood. Furthermore, it is known that the loss of renal function is strongly associated with a pro-inflammatory milieu and an impaired immune system, which is expected to hamper the regenerative potential.
The aim of this project is to gain insight in the scaffold-induced regenerative processes in healthy and diseased conditions. More specifically, we want to address the key questions; how is the primary immune response coordinated directly after implantation, what is the role of the immune response in vascular remodeling, and what is the effect of a diseased environment on these processes? We will develop a humanized in vitro model that mimics the uremic conditions in ESRD patients to shed light on how these conditions influence the early cell response. Complementary to these in vitro studies, in vivo animal studies will be conducted to study downstream vascular remodeling. These studies will be conducted in collaboration with the InSiTeVx consortium partners.
Researchers: S.E. (Suzanne) Koch
Supervisors: P.Y.W. (Patricia) Dankers, A.I.P.M. (Anthal) Smits, C.V.C. (Carlijn) Bouten
Funded by ZonMW, Life Sciences Health, De Nierstichting