A groundbreaking advancement in cardiac surgery could soon transform the way doctors perform vascular bypass procedures. Scientists at the Wisconsin National Primate Research Center (WNPRC) and the Morgridge Institute for Research at the University of Wisconsin–Madison have successfully developed an off-the-shelf, stem cell-based vascular graft that could significantly improve outcomes for patients requiring bypass surgery.
Published in Cell Reports Medicine, this breakthrough builds upon decades of research in stem cell technology and regenerative medicine, offering a potential solution to the shortage of viable small-diameter vascular grafts.
The Need for an Alternative to Traditional Bypass Grafts
Cardiovascular disease remains one of the leading causes of death globally, with coronary artery bypass grafting (CABG) being a common surgical intervention. However, current options for small-diameter vascular grafts are limited:
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- Autologous Grafts: Surgeons typically harvest blood vessels from the patient’s own body, but this can be invasive, painful, and limited by pre-existing conditions.
- Donor Grafts: Using vessels from another person can lead to immune rejection and supply shortages.
- Synthetic Grafts: While synthetic materials work well for large vessels, they have high failure rates when used in smaller arteries.
This study aimed to create a readily available, bioengineered vascular graft that could eliminate these limitations.
Building the Stem Cell-Based Vascular Graft
The researchers focused on developing a small-diameter vascular graft using arterial endothelial cells (AECs) derived from human pluripotent stem cells. These cells have the ability to:
- Self-renew indefinitely, providing an unlimited supply of vascular cells.
- Differentiate into any human cell type, allowing scientists to create functional artery-like structures.
The graft itself was constructed using expanded polytetrafluoroethylene (ePTFE), a porous material also used in Teflon. The challenge, however, was making the surface of the ePTFE suitable for cell adhesion.
Overcoming Material Challenges with Bioengineering
Because ePTFE is hydrophobic and repels water, researchers needed to modify its surface to allow the endothelial cells to attach. They found inspiration in mussels, which produce adhesive proteins to stick to wet surfaces.
Using this insight, the team developed a dual-layer coating consisting of:
- Dopamine, a key component of mussel adhesive proteins, to help anchor the cells.
- Vitronectin, a human cell adhesion protein, to enhance endothelial cell attachment and stability.
The coated grafts were tested under physiological flow conditions, mimicking real-life blood circulation. The bioengineered cells remained uniformly distributed and stable, proving their potential viability for surgery.
Testing the Grafts in Non-Human Primates
To evaluate real-world performance, the researchers implanted the bioengineered grafts into the femoral arteries of Rhesus macaques—a common model for human vascular research.
A key concern in vascular grafts is immune rejection, which occurs when the body recognizes the transplanted tissue as foreign. This process is primarily regulated by the major histocompatibility complex (MHC) proteins, which help the immune system differentiate between self and non-self cells.
The study tested three different graft types:
- Naked ePTFE grafts (without cells)
- Grafts lined with AECs expressing MHC (wildtype)
- Grafts lined with AECs lacking MHC (double knockout)
Findings and Surprising Results
The researchers monitored the grafts biweekly using ultrasound imaging, looking for signs of failure such as stenosis (narrowing), cell wall thickening, or thrombosis (clotting).
- MHC double knockout grafts (lacking immune markers) had a 50% failure rate—suggesting that removing MHC proteins did not prevent immune rejection. Researchers suspect natural killer (NK) cells played a role in attacking the grafts.
- MHC wildtype grafts maintained normal function for six months, proving to be the most successful.
- Over time, the wildtype grafts became populated with host endothelial cells, indicating that they could integrate into the body’s vascular system for long-term success.
These results suggest that completely removing MHC expression may not be the best approach, but carefully engineered grafts with functional endothelial cells could work effectively.
The Future: Human Trials and Clinical Applications
This research represents a significant step toward clinical translation. According to Dr. Samuel Poore, chair of the Division of Plastic Surgery at UW–Madison, this innovation has the potential to:
- Expand surgical options for patients who lack viable autologous vessels.
- Reduce surgical complications and morbidity by eliminating the need for vessel harvesting.
- Improve success rates in plastic, reconstructive, vascular, and cardiac surgery.
The next phase of research will involve refining the graft design, conducting long-term studies, and preparing for human clinical trials.
Conclusion: A Game-Changer for Cardiac Surgery
Stem cell-derived vascular grafts represent a paradigm shift in cardiovascular surgery. By combining bioengineering, regenerative medicine, and immunology, researchers have paved the way for a scalable, off-the-shelf solution that could benefit millions of patients worldwide.
With further development, this breakthrough could revolutionize the treatment of cardiovascular disease—reducing surgery risks, expanding treatment options, and improving patient outcomes for years to come.
