In a new study, lab-made heart valves were shown to grow along with their recipient when implanted into lambs for a year, making a new alternative possible for thousands of paediatric patients who need replacement heart valves.
Researchers from the University of Minnesota Twin Cities’ College of Science and Engineering and the Medical School published the results in Science Translational Medicine. The production procedure for the valves has also been patented and licensed to the University of Minnesota startup company Vascudyne, Inc.
Compared to currently used animal-derived valves, these new valves also showed reduced calcification and improved blood flow when tested in the same growing lamb model. Current solutions for children involve prosthetic valves, but these calcify over time and cannot grow with the patient. This requires up to five open-heart surgeries to replace them as the children grow towards adulthood, involving considerable risk and expense, as well as demanding lifelong anticoagulation therapy.
“This is a huge step forward in paediatric heart research,” commented senior researcher Robert Tranquillo, a University of Minnesota professor in the Departments of Biomedical Engineering and the Department of Chemical Engineering and Materials Science. “This is the first demonstration that a valve implanted into a large animal model, in our case a lamb, can grow with the animal into adulthood. We have a way to go yet, but this puts us much farther down the path to future clinical trials in children. We are excited and optimistic about the possibility of this actually becoming a reality in years to come.”
Using a combination of tissue engineering and regenerative medicine, they were able to grow the heart valves. Implementing a tissue engineering technique they had previously developed, they grew tube-like structures out of skin cells. This involved combining the skin cells in fibrin, and providing nutrients in a bioreactor. After washing the skin cells out with detergent, the researchers were left with a collageneous matrix which would not provoke an immune response when implanted. They then sewed and trimmed three of these tubes together to make a 19mm diameter heart valve-like structure.
“After these initial steps, it looked like a heart valve, but the question then became if it could work like a heart valve and if it could grow,” Tranquillo said. “Our findings confirmed both.”
The valves grew from 19mm to 25mm over a year, and showed little of the calcification or clotting associated with prosthetic valves, while performing better than animal-derived valves.”We knew from previous studies that the engineered tubes have the capacity to regenerate and grow in a growing lamb model, but the biggest challenge was how to maintain leaflet function in a growing valved conduit that goes through 40 million cycles in a year,” said lead researcher Zeeshan Syedain, a University of Minnesota senior research associate in Tranquillo’s lab. “When we saw how well the valves functioned for an entire year from young lamb to adult sheep, it was very exciting.”
The next steps are to implant the valve into the right ventricle of the heart to see how it performs, and apply for FDA approval to proceed to human trials.
Source: Medical Xpress
Journal information: Zeeshan H. Syedain et al, Pediatric tri-tube valved conduits made from fibroblast-produced extracellular matrix evaluated over 52 weeks in growing lambs, Science Translational Medicine (2021). DOI: 10.1126/scitranslmed.abb7225
