New tissue-engineered blood vessel replacements one step closer to human trials

Researchers at the University of Minnesota have created a new lab-grown blood vessel replacement that is composed completely of biological materials, but surprisingly doesn't contain any living cells at implantation. The vessel, that could be used as an "off the shelf" graft for kidney dialysis patients, performed well in a recent study with nonhuman primates.

It is the first-of-its-kind nonsynthetic, decellularized graft that becomes repopulated with cells by the recipient's own cells when implanted. The discovery could help tens of thousands of kidney dialysis patients each year. The grafts could also be adapted in the future for use as coronary and peripheral bybass blood vessels and tubular heart valves.

The research was published today as the cover story in Science Translational Medicine, an interdisciplinary medical journal by the American Association for the Advancement of Science (AAAS). The University of Minnesota has also licensed the technology.

More than 100,000 people in the United States begin hemodialysis each year to treat kidney disease and more than 400,000 people are being treated with life-saving hemodialysis nationwide, according to the U.S. Renal Data System Annual Data Report. An arteriovenous fistula, which connects an artery to a vein in the arm, is currently the preferred mode of blood vessel access for hemodialysis. However, 30-50 percent of patients experience complications and need to connect the vein and artery using an artificial tube, called an arteriovenous graft.

Currently, these artificial grafts are made of synthetic materials that are prone to clotting, infection and other complications. Grafts grown in the lab from cells and biological materials could cause fewer adverse reactions, but living tissues aren't stable for long-term storage and could induce an immune response unless the patient's own cells were used, both being barriers to commercialization and clinical use.

In this pre-clinical study, University of Minnesota researchers generated vessel-like tubes in the lab from post-natal human skin cells that were embedded in a gel-like material made of cow fibrin, a protein involved in blood clotting. Researchers put the cell-populated gel in a bioreactor and grew the tube for seven weeks and then washed away the cells over the final week. What remained was the collagen and other proteins secreted by the cells, making an all-natural, but non-living tube for implantation.

"We harnessed the body's normal wound-healing system in this process by starting with skin cells in a fibrin gel, which is Nature's starting point for healing," said University of Minnesota Department of Biomedical Engineering Professor Robert Tranquillo who led the study. "Washing away the cells in the final step reduces the chance of rejection. This also means the vessels can be stored and implanted when they are needed because they are no longer a living material. In the future, thousands of the lab-grown vessels could be made from a small skin biopsy from one donor and then stored on the shelf for when they are needed by patients."

To test the vessels, the researchers implanted the 15-centimeter-long (about 5 inches) lab-grown grafts into adult baboons donated by Mayo Clinic as it was closing down its primate facility. Six months after implantation, the grafts grossly appeared like a blood vessel and the researchers observed healthy cells from the recipients taking up residence within the walls of the tubes. None of the grafts calcified and only one ruptured, which was attributed to inadvertent mechanical damage with handling. The grafts after six months were shown to withstand almost 30 times the average human blood pressure without bursting. The implants showed no immune response and resisted infection. In addition, the grafts withstood repeated needle punctures by self-healing, which would be a necessary process for patients undergoing long-term dialysis.

"This pre-clinical trial was extremely important to us," Tranquillo said. "In previous studies, we implanted vessels in sheep, but we needed to test them in a more human-like model before risking human lives because the success of our material depends on the ability of the recipient to recellularize it into a living tissue without immune response, which might have failed in a human even though it succeeded in a sheep."

With the success of this study, Tranquillo and the team will seek FDA approval for clinical trials in children with pediatric heart defects since they recently reported a study in Nature Communications that this material is also capable of growing.

The research was funded by a private grant the John and Nancy Lindahl Children's Heart Research Innovators Fund and the University of Minnesota Center for Translational Medicine.

Zeeshan H Syedain, Melanie L Graham, Ty B Dunn, Timothy O'Brien, Sandra L Johnson, Robert J Schumacher, Robert T Tranquillo.
A completely biological “off-the-shelf” arteriovenous graft that recellularizes in baboons.
Science Translational Medicine, Vol. 9, Issue 414. doi: 10.1126/scitranslmed.aan4209.

Most Popular Now

Fasenra (benralizumab) receives US FDA approval fo…

AstraZeneca and its global biologics research and development arm, MedImmune, announced that the US Food and Drug Administration (FDA) has approved Fasenra (benralizumab)...

A great place to do great things: Developing game-…

Science has spoken: Abbott (NYSE: ABT) is, again, among the best science-based companies to work for in the world. For the 14th year, the journal Science today recognized...

Alzheimer's disease might be a 'whole body' proble…

Alzheimer's disease, the leading cause of dementia, has long been assumed to originate in the brain. But research from the University of British Columbia and Chinese scie...

Cancer cells destroyed with dinosaur extinction me…

Cancer cells can be targeted and destroyed with the metal from the asteroid that caused the extinction of the dinosaurs, according to new research by an international col...

Novartis confirms leadership in multiple sclerosis…

Novartis today announced it will present 54 scientific abstracts from across its multiple sclerosis (MS) research portfolio at the 7th Joint European and Americas Committ...

Amgen and Novartis announce expanded collaboration…

Amgen (NASDAQ:AMGN) and Novartis announced an expanded collaboration with the Banner Alzheimer's Institute (BAI) to initiate a new trial - the Alzheimer's Prevention Init...

Transplanted hematopoietic stem cells reverse dama…

Researchers at University of California San Diego School of Medicine report that a single infusion of wildtype hematopoietic stem and progenitor cells (HSPCs) into a mous...

Novartis announces the planned acquisition of Adva…

Novartis announced today, that it has entered a memorandum of understanding with Advanced Accelerator Applications (AAA) under which Novartis intends to commence a tender...

'Precision Medicine' may not always be so precise

Precision Medicine in oncology, where genetic testing is used to determine the best drugs to treat cancer patients, is not always so precise when applied to some of the w...

New tissue-engineered blood vessel replacements on…

Researchers at the University of Minnesota have created a new lab-grown blood vessel replacement that is composed completely of biological materials, but surprisingly doe...

China's out of control 'silent killer' affects one…

More than one-third of adults in China have high blood pressure - often dubbed the "silent killer" for its lack of symptoms - but only about one in 20 have the condition ...

MSD Innovation Factory is looking for digital solu…

MSD is looking for innovators to solve 7 health-related challenges. One of them seeks to support anaesthesiologists with their continuous education (e.g. at the operation...

Pharmaceutical Companies

[ A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Z ]