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[Modified endothelial cells in graft vasculopathy]
1Klinik für Thorax-, Herz- und Gefässchirurgie Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Laue@thg.mh-hannover.de
Insights
Modifying endothelial cells ex vivo offers a promising strategy to prevent graft vasculopathy in coronary artery bypass grafting and transplanted hearts, potentially reducing re-do operations and improving long-term outcomes.
Area of Science:
- Vascular Biology and Regenerative Medicine
- Cardiovascular Surgery
- Immunology
Context:
- Venous bypass graft occlusion is a primary cause of re-do coronary revascularization surgery.
- Coronary artery disease significantly limits the long-term success of cardiac transplantation.
- Endothelial dysfunction, driven by mechanical injury and pressure, leads to intimal hyperplasia and graft failure.
Purpose:
- To explore ex vivo modification of endothelial cells as a therapeutic approach for graft vasculopathy.
- To investigate the use of acellularized xenogenic matrices for vascular graft development.
- To assess gene therapy strategies for enhancing endothelial cell function in grafts.
Summary:
- Seeding endothelial cells onto artificial or bioartificial matrices is feasible.
- Recellularizing acellularized xenogenic matrices with autologous cells offers a potential solution for durable vascular and valvular grafts.
- Gene modification of endothelial cells, e.g., nitric oxide overexpression or matrix metalloproteinase inhibition, presents a novel therapeutic avenue.
Impact:
- Potential to reduce re-do operations in coronary revascularization.
- Improved long-term survival and function of transplanted hearts.
- Development of more durable vascular and valvular grafts for clinical use.
- Promising preclinical results in large animal studies suggest imminent clinical trials.
Abstract:
Occlusion of venous bypass grafts after coronary revascularization grafting represents the main reason for re-do operations. Arterial pressure as well as mechanical injury of the venous wall lead to endothelial dysfunction, causing intimal hyperplasia with luminal stenosis and eventually occlusion. In the transplanted heart, coronary artery disease limits the long-term success of cardiac transplantation. The disease is characterized by the interaction of activated immunologic cells and donor epicardical and microvascular endothelium. The ex vivo modification of endothelial cells may offer a therapeutic option to overcome both kinds of graft vasculopathy. Seeding of human endothelial cells on artificial and bioartificial acellularized vessel matrices has proven possible. The use of xenogenic matrices initially acellularized and recellularized with autologic endothelial cells and myofibroblasts may help to overcome the lack of vascular and valvular grafts with long durability. In addition, gene therapeutic methods to modify the function of such endothelial cells may offer a new therapeutic strategy, such as over-expression of nitric monoxide or inhibition of matrix metalloprotinases. First results of large animal studies show promising results and may lead to the first clinical trials in the near future.