Development of patient-specific small diameter vascular grafts from induced pluripotent stem cells

Small diameter blood vessel (SDBV) substitutes for the replacement of vessel blockage due to atherosclerosis are of great research and clinical interests. Current SDBV grafts have suffered from low patency rate, due to thrombosis and intimal hyperplasia. We propose to address the problem by generating patient-specific SDBV grafts using tissue engineering strategies. We hypothesize that induced pluripotent stem (iPS) cells derived vascular cells from peripheral arterial disease (PAD) patients can be used to generate cellbased grafts with functionality comparable to normal vessels. To test this hypothesis, we will firstly determine whether iPS derived endothelial cells (ECs) and smooth muscle cells (SMCs) from patients with PAD can function as viable cell sources. We will then work on arterial scaffolds generated by decellularization of rat aortas with chemical modification to prevent thrombosis. Patient-specific vascular cells will then be incorporated to the scaffold to form a confluent EC inner layer and SMC outer layer, with functionality tested comparing with normal vessels. With the tissue engineered SDBV grafts, we are expected to reproducibly generated patient-specific grafts, and achieve the functionality similar to that of autologous grafts, in order to solve the tissue shortage problem.