We grow together with the owner
Heart valves created in the laboratory can grow together with the recipient
Anna Yudina, "Scientific Russia"
The revolutionary discovery could potentially reduce the number of heart valve replacement surgeries in children, according to a press release Lab-created heart valves can grow with the recipient, citing Science Translational Medicine (Syedain et al., Pediatric tri-tube valved conduits made from fibroblast-produced extracellular matrix evaluated over 52 weeks in growing lambs).
A new study conducted by specialists from the University of Minnesota Twin Cities College of Science and Engineering and Medical School shows for the first time that laboratory-created heart valves implanted in young lambs are able to grow inside the recipient within a year. The valves also showed reduced calcification and improved blood flow function compared to animal-derived valves currently used in testing on a growing lamb model.
If confirmed in humans, these new heart valves can prevent the need for repeated valve replacement operations in thousands of children who are born with congenital heart defects every year. The valves can also be stored for at least six months, which means they can provide surgeons with a ready-made treatment option.
"This is a huge step forward in pediatric heart research," said Robert Tranquillo, senior researcher on the study and professor in the Department of Biomedical Engineering and the Department of Chemical Engineering and Materials Science at the University of Minnesota. – This is the first demonstration that a valve implanted in a model of a large animal, in our case a lamb, can grow together with the animal. This significantly advances us on the way to future clinical trials in children. We are excited and optimistic about the possibility that this will actually become a reality in the coming years."
Currently, researchers have not been able to develop a heart valve that could grow and maintain function for pediatric patients. The only acceptable options for these children with heart defects are valves made from chemically treated animal tissues, which often become non-functional due to calcification and require replacement because they do not grow with the child. These children often have to undergo up to five (or more) open-heart surgeries until a mechanical valve is implanted in adulthood. In addition, they have to take anticoagulants all their lives.
In this study, Tranquillo and his colleagues used a hybrid of tissue engineering and regenerative medicine to create growing heart valves. During an eight-week period, they used a specialized tissue engineering method that they had previously developed to create vessel-like tubes in the laboratory from skin cells from a postpartum donor. To develop the tubes, the researchers combined donated sheep skin cells in a gelatin-like material called fibrin in the shape of a tube, and then, using a bioreactor, provided the nutrients needed for cell growth.
The researchers then used special detergents to wash off all the sheep cells from the tissue-like tubes, leaving a cell-free collagen matrix that does not cause an immune response during implantation. The blanks can be stored and implanted without requiring individual growth using recipient cells.
The next step was to precisely stitch three of these tubes (about 16 mm in diameter) together into a closed ring. The researchers then trimmed them slightly to create flaps that mimic a structure similar to a heart valve with a diameter of about 19 mm.
"After these initial steps, it looked like a heart valve, but then the question arose whether it could work as a heart valve and whether it could grow," Tranquillo said. "Our results confirmed both facts."
This second generation of three-tube valves was implanted into the pulmonary artery of three lambs. After 52 weeks, the valve regenerated, as its matrix was populated with cells of the recipient lamb, and the diameter increased from 19 mm to a physiologically normal valve by about 25 mm. The researchers also noted an increase in the length of the valve flaps by 17-34% according to ultrasound. In addition, the researchers have shown that three-tube valves work better than existing valves of animal origin, with virtually no calcification or blood clotting, which were observed in other valves after implantation to lambs of the same age.
"We knew from previous studies that engineered tubes have the ability to regenerate and grow in a growing lamb model, but the biggest challenge was how to maintain the flap function in a growing valve channel that goes through 40 million cycles per year," said Zishan Siedine, lead researcher of the study and senior researcher at the University of Minnesota in the Tranquillo lab. – When we saw how well the valves work throughout the year during the development of a young lamb into an adult ram, it was very interesting."
Tranquillo said the next steps are to implant a three–tube valve directly into the right ventricle of the heart to simulate the most common surgical intervention, and then begin the process of requesting permission from the U.S. Food and Drug Administration (FDA) for human clinical trials over the next few years.
"If we can ever approve these valves for children, it will have such a big impact on children suffering from heart defects and their families who have to deal with huge stress from multiple surgeries," Tranquillo said. "We could potentially reduce the number of surgeries these children will have to undergo, from five to one – it's a dream."
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