Heart :: Major advance in tissue engineering growing heart valves

For the first time, researchers have successfully used a rabbit’s cells to grow heart-valve-shaped tissue inside the animal’s body, according to research reported at the American Heart Association’s Scientific Sessions 2006.

The process may someday make it possible to grow rejection-proof replacement valves for humans using a person’s own cells, a process called autologous tissue engineering.

“It’s the first fabrication of an autologous heart valve inside a living body,” said Kyoko Hayashida, M.D., lead author of the study and a research fellow at the National Cardiovascular Center Research Institute in Osaka, Japan, and at the Kyoto Prefecture University of Medicine.

“We created an autologous valved-conduit through a simplified and less costly process carried out in living bodies,” she said. “If every body organ could be recreated by using autologous cells, it would solve the current shortage of donated organs available for transplantation and the use of costly and harmful anti-rejection drugs.”

The heart has four chambers with valves between each. When they work properly, the four heart valves — the tricuspid, pulmonic, mitral and aortic valves — open and close to keep blood flowing in only one direction between the chambers, between the heart and lungs, and from the heart to the rest of the body, Hayashida said.

When the valves are damaged, from either malformations before birth or later changes caused by infections or aging, they don’t open and close properly, putting stress on the circulatory system.

“In body” tissue-engineering takes advantage of the body’s tissue encapsulation phenomenon, in which the body’s cells naturally surround implanted foreign materials, she said.

Damaged or deformed heart valves are replaced with donated valves, mechanical heart valves or valves from other species such as pigs (xenografts).

All of those approaches have drawbacks, researchers said. Mechanical valves are prone to blood clots. As a result, patients with mechanical valves must take anti-clotting drugs for the rest of their lives. Valves from human or animal donors may gradually deteriorate because they have no living cell components and they can’t self-repair.

Furthermore, none of those replacement heart valves can grow as the recipient’s body does, making them problematic for use in children born with faulty heart valves, Hayashida said.

“Tissues made from the patient’s own cells hold the promise of growing along with the patient,” she said.

Hayashida said that her research group developed plastic molds that included three flap-like leaflets that mimic the flaps of a heart valve. The leaflets contained a tiny opening, less than one millimeter wide. An elastic-like conduit scaffold, repeatedly pierced by a laser to give it a sponge-like texture, held the leaflets in place.

The entire apparatus is just over a centimeter long with a diameter of less than a centimeter, making it possible to implant up to five molds in a layer of fat on the rabbits’ backs without bothering the rabbits, who went about their usual activities, she said.

The laser-produced holes allowed the rabbits’ cells to infiltrate the molds and grow all around them, she said. After one month, the researchers removed the molds from the rabbits, again without incident to the animals. Hayashida and her colleagues then removed the outer mold, and left intact the heart-valve-shaped inner mold, now surrounded by tissue and attached by more new tissue to the donut-shaped conduit of tissue surrounding it.

They implanted 10 molds: five in the first rabbit, three in the second rabbit and two in the third. They reported a 50 percent success rate overall (in five of 10 attempts): two of five in the first rabbit, two of three in the second and one of two in the third.

Although the valve conduits did not have the same cell layers as natural heart valves, they functioned in a similar way when researchers performed flow studies in test tubes.

Future research will investigate whether the valves can resist the fluid pressures encountered by native heart valves without degradation. The researchers also plan to further evaluate the engineered valve’s function when implanted in the body, as well as its potential for growth, self-repair and regeneration in the body, she said.

In a poster session, one of Hayashida’s colleagues, Taiji Watanabe, M.D., reported that the same autologous tissue engineering approach was used to create small-caliber (less than 2 millimeter diameter) blood vessel grafts, called Biotubes. Biotubes performed like native arteries when implanted in the rabbits in which they were grown.

The biotubes also withstood high pressures and showed no signs of rupture during three months of follow-up after implantation, Watanabe said.

Other co-authors are Tomonori Oie, M.S.; Yosihiro Okamoto, M.S.; Hatsue Ishibashi-Ueda, M.D., Ph.D.; Tsutomu Tajikawa, Ph.D.; Kenkichi Oba, Ph.D.; Osamu Sakai M.D.; Keiichi Kanda, M.D., Ph.D.; Hitoshi Yaku, M.D., Ph.D.; and Yasuhide Nakayama, Ph.D.

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