Todd McAllister, Ph.D., president and CEO of Cytograft Tissue Engineering, discussed the company’s technology for building vascular grafts using autologous cells. He said that Cytograft’s technology, called tissue engineering by self assembly (TESA), produces versatile tissues with high mechanical strength that are free of synthetic scaffolding or exogenous biomaterials, thereby avoiding the risk of immunologic responses or rejection.
In 2007, the company reported clinical results using its Lifeline™ graft in kidney dialysis patients in whom conventional hemodialysis access shunts had failed. Conventionally, such arteriovenous (AV) shunts are made by creating a “short circuit” between an artery and a vein to accelerate blood flow in order to shorten hemodialysis times. These conduits, Dr. McAllister said, must withstand extraordinarily high flow rates and are punctured six times weekly during the hemodialysis sessions.
Ideally, this short circuit can be created using the patient’s own tissue by connecting a vein directly to an artery. Over time, however, the shunts fail, necessitating the use of synthetic materials such as Gortex or chemically modified animal veins to re-create the shunt. The synthetic grafts demonstrate significantly higher failure rates than native tissue.
“Despite the relatively low number of hemodialysis patients in the U.S., maintenance of hemodialysis access grafts absorbs more than 1 percent of Medicare’s entire budget, making AV access a multibillion dollar problem.”
As reported in The Lancet, Dr. McAllister and his colleagues implanted Lifeline grafts in 10 patients with end-stage renal disease who had been receiving hemodialysis through an access graft that had a high probability of failure, and who had experienced at least one previous access failure. Completely autologous tissue-engineered vascular grafts were grown in culture supplemented with bovine serum, implanted as arteriovenous shunts, and assessed for both mechanical stability during the safety phase and effectiveness after hemodialysis.
The grafts are created using fibroblasts removed from individual patient’s skin, which are then grown in tissue culture to produce a sheet composed of the cells and proteins such as collagen and elastin produced by the cells. The sheet is then rolled up into a multilaminate roll and allowed to fuse into a uniform tissue. The inner layers are then air dried and a second living sheet is wrapped around the outside. Decellularization of the inner layers prevents migration of any cells into the interior lumen of the vessel. The patient’s own endothelial cells are then added to the inside of the nascent vessel to prevent the vessel from clotting.
In the clinical trial, three grafts failed within the safety phase, consistent the company said, with expected failure rates in this high-risk population. One patient was withdrawn from the study due to unrelated gastrointestinal bleeding that occurred immediately prior to implantation and another patient died of unrelated causes during the study safety period. The five remaining patients had grafts that continued to function for hemodialysis 6 to 20 months following implantation and a total of 68 patient-months of patency. Of note, Dr. McAllister said, is that the complication rate for these surviving grafts was significantly lower compared to the standard of care.
Overall, primary patency was maintained in seven of the remaining nine patients, one month after implantation and in five of the remaining eight patients, six months after implantation.