In patients who must receive dialysis to accommodate failing kidneys, ports are placed in their blood vessels, and a vein and an artery are tied together. The name for the connection of an artery and a vein is a Cimino-Brescia fistula. Such fistulas are necessary for dialysis, and they are usually made in the arm. Since blood, like other fluids takes the path of least resistance, such fistulas generate high volume flow rates. Blood flow will prefer the fistula over capillary beds, which are high resistance flow areas. Also, native blood vessels are usually used to generate these fistulas because they are less likely to narrow and fail. Unfortunately, these surgical connections tend to fail. Worse still, they cannot be used in some patients because of the bad shape of their vascular system. Therefore, the answer in those cases is a graft. That seems onerous and likely to fail too. Is there a better way?
Zeeshan H. Syedain and his coworkers from the laboratory of Robert Tranquillo at the University of Minnesota have used tissue engineering approach to generate vascular grafts from fibrin scaffolds and skin-based human fibroblasts. In short, Tranquillo and his colleagues have made “off-the-shelf” blood vessels that were grown in the laboratory and do not have any living cells. Such lab-grown vessels might serve as blood vessel replacements for hard-up dialysis patients and others. Tranquillo and his group published their findings in the journal Science Translational Medicine.
To make blood vessel substitutes, Tranquillo and others embedded human skin cells in a gel-like material made of cow fibrin. This concoction was grown in a bioreactor for seven weeks, after which, the cells were washed away. This left vessel-like tubes made of collagen and other proteins secreted by the cells.
Tranquillo said of this study, “We harnessed the body’s normal wound-healing system in this process by starting with skin cells in a fibrin gel, which is Nature’s starting point for healing.” He continued, “Washing away the cells in the final step reduces the chance of rejection. This also means the vessels can be stored and implanted when they are needed because they are no longer a living material.”
The vessel-like tubes looked like blood vessels, and they lacked any human cells. Therefore, the immune system should not reject them if they were implanted into a human body. However, can they function as blood vessels? To address this concern, Tranquillo and others implanted their laboratory-produced tubes into adult baboons. Six months after transplantation, the engrafted vessels looked like blood vessels and healthy cells from the recipient had grown into them and seemed to adapt to them without any ill effects. These laboratory-made vessels could withstand 30 times the average human blood pressure without bursting. Additionally, there was no indication of an immune response and the grafts even self-healed when punctured with a needle.
Tranquillo and the team are in the process of FDA approval to test their synthetic blood vessels in clinical trials. In particular, Tranquillo and his team would like to test them in children with pediatric heart defects.