Repeated surgery is a bittersweet topic in the Congenital Heart defects community.
On the one hand it means that the previous surgery was successful, that your child has grown and progressed, but on the other hand, it means new trauma, new anxiety, and new risks.
The university of Minnesota lead a new study in which their biomedical engineers, bioengineered artificial blood vessels in the lab and implanted these blood vessels in young lambs. These artificial blood vessels are capable of growth within the recipient. These blood vessels have only been tested in lambs, but if confirmed in humans, these new vessel grafts would prevent the need for repeated surgeries in some children with congenital heart defects.
The study was published in the journal Nature Communications.
One of the greatest challenges in vessel bioengineering is designing a vessel that will grow with its new owner.
In this study, University of Minnesota Department of Biomedical Engineering Professor Robert Tranquillo and his colleagues generated vessel-like tubes in the lab from a post-natal donor’s skin cells. The cells were removed the cells to minimize the chance the recipient body rejecting the artificial blood vessels.
Because the biological material (i.e. the cells) were removed from the vessels, the vessels can be stored and implanted when they are needed, without the need for customized cell growth of the recipient. When these vessels were implanted in the recipient lamb, the tube was repopulated by the recipient’s own cells allowing it to grow.
“This might be the first time we have an ‘off-the-shelf’ material that doctors can implant in a patient, and it can grow in the body,” Tranquillo said. “In the future, this could potentially mean one surgery instead of five or more surgeries that some children with heart defects have before adulthood.”
The material for this study was developed through a combination of sheepskin cells in a gelatin-like material, called fibrin, in the form of a tube and then rhythmically pumped in nutrients necessary for cell growth using a bioreactor for up to five weeks. The pumping bioreactor is a necessary part of the process as it provided both nutrients and “exercise” to strengthen and stiffen the tube. Another key function of the bioreactor, developed with Zeeshan Syedain, a senior research associate in Tranquillo’s lab, was to ensure that the artificial vessels are stronger than a native artery so it wouldn’t burst in the patient, cause hemorrhage.
Special detergents to wash away all the sheep cells, leaving behind a cell-free matrix that does not cause immune reaction when implanted. During the strudy, the artificial vessels were grafted to replace portions of the pulmonary artery of 5-week old three lambs. The success of the study was proven when the lamb’s own cells populated the artificial vessel. As the lamb’s cells populate the matrix during the lamb’s development, the artificial vessels with not only grow inside the recipient but also bend and conform to the necessary shape as a native vessel would have. This means that a vessel replacement will not be necessary as the lambs grow into adulthood.
“What’s important is that when the graft was implanted in the sheep, the cells repopulated the blood vessel tube matrix,” Tranquillo said. “If the cells don’t repopulate the graft, the vessel can’t grow. This is the perfect marriage between tissue engineering and regenerative medicine where tissue is grown in the lab and then, after implanting the decellularized tissue, the natural processes of the recipient’s body makes it a living tissue again.”
A report on the study states: “At 50 weeks of age, the sheep’s blood vessel graft had increased 56 percent in diameter and the amount of blood that could be pumped through the vessel increased 216 percent. The collagen protein also had increased 465 percent, proving that the vessel had not merely stretched but had actually grown. No adverse effects such as clotting, vessel narrowing, or calcification were observed.”
“We saw growth and none of the bad things happened,” Tranquillo said. “The results are very encouraging.”
The findings of study were first published in September 2016. It was stated that the next step would be to request approval for human trials. Upon Heart Kids South Africa’s last query in January 2017, no human trials had been planned yet. We will keep in contact with the research team with regards to their plans for future trials.
To read the full research paper entitled “Tissue engineering of acellular vascular grafts capable of somatic growth in young lambs,” visit the Nature Communications website.