Surgeons performing coronary bypass procedures may soon have a new option – bioengineered vascular grafts derived from pluripotent stem cells.
In a study published in Cell Reports Medicine, researchers at the Wisconsin National Primate Research Center (WNPRC) and the Morgridge Institute for Research at the University of Wisconsin–Madison report the successful development of an ‘off-the-shelf’ small-diameter vascular graft that could overcome the limitations of current bypass techniques.
The standard approach for small-diameter vascular grafting in coronary bypass surgery involves autologous vessel harvesting, most commonly from the saphenous vein.
However, this method is constrained by donor site morbidity, vessel quality – especially in patients with comorbidities – and anatomical availability.
Synthetic alternatives, such as polytetrafluoroethylene (ePTFE), have succeeded in large-diameter grafts but have historically struggled with small vessels due to thrombosis and neointimal hyperplasia.
Senior co-author Igor Slukvin, professor of pathology and laboratory medicine at the WNPRC, said: ‘Although synthetic vascular grafts have been successfully used in clinics for large vessel repair, sources for small-diameter vessels, most commonly used for the coronary bypass surgery, are limited. This work is important in advancing stem cell technologies for bioengineering vascular grafts for cardiac vessel repair and their clinical translation.’
The research team addressed these challenges by generating arterial endothelial cells (AECs) from human pluripotent stem cells (hPSCs) and developing a method to seed them onto an ePTFE scaffold.
Co-author John Maufort, formerly of the Thomson Lab at the Morgridge Institute, said: ‘Patient-specific cell therapies can be cost-prohibitive and time-consuming. We wanted to develop an off-the-shelf small-diameter arterial graft that can be readily used in clinical settings.’
The team turned to a biomimetic approach inspired by mussel adhesive proteins to overcome ePTFE’s hydrophobic properties.
Using a combination of dopamine and vitronectin, they created a dual-layer coating that allowed AECs to adhere robustly to the graft surface. This bioengineered lining was subjected to physiological flow testing, confirming its stability and uniformity under hemodynamic conditions.
To evaluate long-term graft performance, the team implanted the constructs into the femoral arteries of Rhesus macaques, a widely accepted translational model for cardiovascular research.
They compared three groups:
• Unseeded ePTFE grafts
• Grafts seeded with wild-type AECs expressing major histocompatibility complex (MHC)
• Grafts seeded with MHC-knockout AECs.
Surprisingly, despite expectations that MHC knockout would reduce immune rejection, these grafts exhibited a 50% failure rate.
Conversely, the MHC wild-type grafts showed 100% patency over six months. Notably, the endothelial lining was repopulated by host cells, indicating a mechanism for long-term integration and durability.
The results suggest that stem cell-derived arterial grafts have substantial potential for use in coronary bypass and other vascular surgeries.
The research paves the way for future clinical trials to validate these findings in human subjects, potentially transforming the standard of care in vascular surgery.
