ABSTRACT
Small caliber synthetic vascular grafts are commonly used for bypass surgery and dialysis access sites but have high failure rates because of neointima formation and thrombosis. Seeding synthetic grafts with endothelial cells (ECs) provides a biocompatible surface that may prevent graft failure. However, EC detachment following exposure to blood flow still remains a major obstacle in the development of biosynthetic grafts. We tested the hypothesis that induced expression by the seeded EC, of vascular endothelial growth factor165 (VEGF165) and of fibulin-5, an extracellular matrix glycoprotein that has a crucial role in elastin fiber organization and increase EC adherence to surfaces, may improve long-term graft patency. Autologous ECs were isolated from venous segments, and were transduced with retroviral vectors expressing fibulin-5 and VEGF165. The modified cells were seeded on expanded polytetrafluoroethylene (ePTFE) grafts and implanted in a large animal model. Three months after transplantation, all grafts seeded with modified EC were patent on a selective angiography, whereas only a third of the control grafts were patent. Similar results were shown at 6 months. Thus, seeding ePTFE vascular grafts with genetically modified EC improved long-term small caliber graft patency. The biosynthetic grafts may provide a novel therapeutic modality for patients with peripheral vascular disease and patients requiring vascular access for hemodialysis.
Subject(s)
Endothelial Cells/transplantation , Extracellular Matrix Proteins/therapeutic use , Peripheral Vascular Diseases/therapy , Vascular Endothelial Growth Factor A/therapeutic use , Vascular Grafting/methods , Animals , Endothelial Cells/physiology , Extracellular Matrix Proteins/genetics , Humans , Models, Animal , Rats , Sheep , Vascular Endothelial Growth Factor A/genetics , Vascular PatencyABSTRACT
We present a patient receiving chronic anticoagulant treatment with recurrent and intractable gastrointestinal bleeding due to diffuse angiodysplasia. Following failure of previous medical and surgical treatment, and in light of the patient's need for chronic anticoagulation due to mechanical heart valve, she was treated with somatostatin analogue, octreotide s.c. 100 microg on alternate days for 28 months. Treatment significantly decreased the occurrence of bleeding episodes, the need for hospitalization and blood transfusion requirements despite continued anticoagulant therapy. Octreotide treatment should be considered in patients with refractory gastrointestinal bleeding due to angiodysplasia in particular in those who need anticoagulant treatment.
