A groundbreaking new study led by University of Minnesota Twin Cities researchers from both the College of Science and Engineering and the School of Medicine shows for the first time that lab-created heart valves were able to engaged in young lambs for a year of growth within the recipient. The valves also showed a smaller calcification and better blood flow function compared to valves derived from currently used animals when tested in the same growing lamb model.
If proven in humans, these new heart valves could eliminate the need for recurrent valve surgeries in thousands of children born each year with congenital heart problems. The valves can also be stored for at least six months, which means they could give surgeons an “off the shelf” option for their treatment.
The study was published today in Science Translational Medicine, an interdisciplinary medical journal by the American Society for the Advancement of Science (AAAS). The valve manufacturing method was also patented and licensed to the University of Minnesota Vascudyne, Inc. startup company. (Stillwater, Minn.).
“This is a major step forward in pediatric cardiac research,” said Robert Tranquillo, senior researcher on the study and professor at the University of Minnesota in the Departments of Biomedical Engineering and the Department of Chemical Engineering and Science Stuthan. “This is the first demonstration that a valve inserted into a large animal model, a lamb in our case, can grow with the animal into adulthood. We still have a way to go, but this is still the case. puts us far further down the path clinically in the future. trials in children. We are excited and optimistic about the potential for this in the years to come. “
Currently, researchers have not been able to develop a heart valve that can grow and maintain function for pediatric patients. The only options accepted by those children with heart defects are valves made of chemically treated animal material that often become useless as a result of calcification and in need of replacement. as they do not grow with the child. These children often require up to five (or more) open heart surgeries until a mechanical joint is inserted as an adult. This requires them to bleed the rest of their lives.
In this study, Tranquillo and his colleagues used a hybrid of tension engineering and regenerative medicine to create the growing heart valves. Over eight weeks, they used a unique tissue engineering device they had previously developed to generate laboratory-like vessel tubes from postnatal donor skin cells. To develop the tubes, researchers combined donor sheep skin cells into a gelatin-like substance, called fibrin, in tube form and then provided nutrients necessary for cell growth using a bioreactor.
The researchers then used special cleansers to wash all the sheep cells away from the cloth-like tubes, leaving behind a cell-free collagenous matrix that does not cause an immune reaction when applied. This means that the tubes can be stored and inserted without the need for normal growth using the recipient’s cells.
The next step was to sew three of these tubes (about 16 mm in diameter) together in a closed ring. The researchers then trimmed them slightly to form leaflets to reproduce a heart valve-like structure about 19 mm in diameter.
“After those initial steps, it was like a heart valve, but then the question arose whether it could operate as a heart valve and whether it could grow,” Tranquillo said. “Our decisions confirmed both.”
This second generation of three-tube valves was inserted into the lung arteries of three lambs. After 52 weeks, the valve regenerated as its matrix came with cells from the receiving lamb, and the diameter increased from 19 mm to a physically normal valve of about 25 mm. The researchers also saw a 17 to 34 percent increase in the length of the valve leaflets as measured from ultrasound images. In addition, researchers showed that the three-tube valves worked better than conventional valves derived from animals with almost none of the calcification or bleeding that the other valves showed after they were put on. apply to lambs of the same age.
“We knew from previous studies that the engineered tubes have the potential to regenerate and grow in a growing lamb model, but the biggest challenge was how to maintain bile duct function in valve burrows. growth that goes through 40 million cycles in a year, ”said Zeeshan Syedain, principal investigator of the study and principal research associate at the University of Minnesota at Tranquillo Laboratory. “When we saw how well the valves worked for a year from young lamb to adult sheep, it was very interesting. “
Tranquillo said the next steps are to insert the three-tube valve directly into the right ventricle of the heart to report the most common surgical repair and then begin the process. seeking approval from the U.S. Food and Drug Administration (FDA) for human clinical trials over the next few years.
“If we can ever agree on these valves for children, it would have such a huge impact on children with heart problems and their families who have to deal with the stress of multiple surgery, said Tranquillo. “We could reduce the number of surgeries these children need from five to one. That’s the dream. “
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Magazine Reference:
Syedain, ZH, et al. (2021) Pediatric trigeminal valve conduction from extracellular matrix produced by fibroblast was evaluated over 52 weeks in growing lambs. Science Translational Medicine. doi.org/10.1126/scitranslmed.abb7225.