Regenerative and reconstructive medicine for vascular disease
- Our group addresses four levels of neovascularization:
- Based on hypotheses and on transcription profiling of growing collaterals we study several molecular circuits that are involved in collateral remodeling and arterial specification such as the prostaglandin E2 and the Notch signaling circuits.
- At a topological level we are studying the complete vascular tree of coronary arteries and their collaterals to study the origin, significance and preferential paths of collaterals. Preliminary evidence suggests that some collaterals form that have no apparent hemodynamic function. This suggests that the paradigmatic hemodynamic control of collateral formation may not be exclusive.
- To define sensitive endpoints of neovascularization and perfusion, we are developing novel MRI and MRA techniques. By focusing on kinetic modeling, novel sequences, novel contrast agents and molecular targeting of contrast agents in preclinical work high magnetic field strengths, 3-7T, we have made significant progress in detection of early neovascularization. Some of these techniques are also being tested in cancer models.
- In a diabetes cohort of patients with critical limb ischemia or severe claudication, MRA is being performed and evaluated as a prognostic indicator of ulcer healing and limb survival. In addition, the MRA outcome is related to response to exercise therapy.
Vascular tissue engineering
It is the aim of our program to develop small caliber vascular grafts with a diameter of 3-4 mm that are suitable for arteriovenous shunting or bypass grafting of below the knee peripheral arteries or proximal coronary arteries. In close collaboration with the Eindhoven Technical University we design these grafts on the basis of PGA scaffolds and human or porcine endothelial cells and myofibroblasts, harvested from venous material. In collaboration with the RWTH Aachen, we are studying novel functionalized biomaterials that are designed to facilitate recruitment and homing of circulating precursor cells. We are studying the ex vivo recruitment of precursor cells to such biomaterials under precisely controlled hemodynamic conditions. In collaboration with Prof Waltenberger, Pharmacell B.V. and Matricel GmbH, we are studying the applicability of collagen scaffolds for vascular tissue engineering.
This program is co-funded by INTACT (Province of Limburg), TeRM (smartmix NOW) and BMM ‘iValve’.