Portfolio at NYU

Posted 01.08.04
Twenty Years to a Whole New Heart

By Lela Moore

Lela Moore
Journalism of Ideas
12/8/03

Approximately 18 people will die today waiting for an organ transplant. Already this year, 3,400 people have died while on the waiting list. The wait-and-see life led by someone in need of a transplant has changed little in the last 10 years.

Cyclosporine, a drug that helps prevent rejection of a transplanted organ, was introduced more than 20 years ago. The drug allowed people to survive longer following transplantation. But transplantation, at its best, can still only afford patients the exchange of a fatal illness for a chronic one.

In Toronto, Dr. Michael Sefton heads the Living Implants From Engineering (LIFE) Initiative, a collective of tissue engineers working to build a human heart. Sefton said the idea for the group came to him "quite literally in a dream," but he called it a logical next step in the biomedical engineering field.

"It began as a small collection of individuals who saw it was time to focus attention on the issues within tissue engineering associated with the organ-donor shortage," said Sefton, a professor of chemical engineering and biomedical engineering at the University of Toronto who also created the Toronto Tissue Engineering Initiative, modeled on a similar program in Pittsburgh.

"We brought together clinicians, scientists, engineers and others at the University of Toronto and related hospitals with a view on tissue engineering and raising its profile within Canada," he said.

Sefton estimates that LIFE Initiative's efforts will result in the creation of an engineered human heart in about 20 years.
It sounds like something out of a science fiction novel, but ultimately this technology could help reduce the organ waiting list to a distant memory.

"Tissue engineering is broadly applicable to every organ and every localized disease that would be benefited by replacing or repairing a body part," said Sefton, who began his career as a tissue engineer before the term was actually coined, in the early 1980s.

During the 1970s, Sefton encapsulated pancreatic islets in pigs so they could be transplanted into humans suffering from diabetes. Sefton has also done research on Parkinson's disease. "The encapsulation technology is thought to have a benefit on a variety of neurological diseases," he said.

Even people who would be out of a job were tissue engineering to revolutionize organ transplantation think that the technology is worth the wait. Miriam Perez is an organ procurement coordinator at the New York Organ Donor Network. She is in charge of taking calls from hospitals with potential organ donors and linking transplant teams to those patients.

"Why should those people die waiting?" she said of the people on the organ wait list.

The board of directors of the United Network for Organ Sharing (UNOS), which maintains the organ wait list, has not issued a formal statement in support of tissue engineering, said Annie Moore, a UNOS spokesperson. "But any scientific advances that could help with the shortage, such as [engineered] organs, could help save lives," Moore said.

Sefton said that the biggest challenge in building a human organ from scratch was creating a vascularization system for blood to flow into the organ and carry waste products away. "How do you supply a big piece of tissue -- a heart muscle, or a liver -- with eh blood supply?" he asked.

Another heart-specific problem he has encountered is creating its electrical system -- ensuring that the heart beats regularly so that it can be pace by a pacemaker when transplanted. "We don't want to create a bunch of arrhythmias," he said.

Currently, organ-transplant recipients must take large doses of immunosuppressant drugs, such as cyclosporine, for the rest of their lives. Eventually, Sefton said, he hoped to engineer an organ made out of the recipient's own tissues or to engineer an organ prewired to work with the patient's immune system -- that is, with its cellular material altered to match the organ recipient's. "One of the benefits of the tissue engineering approach is that you can manipulate the cells before you build the heart," he said. "It's harder to do with the whole heart."

Sefton said the LIFE Initiative team debated at the beginning over which organ they should build first -- which necessitated determining which was most important, he said. "It was hard to decide among the surgeons which organ was the most important," he said. Ultimately, the only organ the team decided not to work with was the brain. "The brain is beyond the scope of what anyone's though about," Sefton said.

However, Sefton said that advancements like those made by a team of scientists at MIT who enabled mice with spinal-cord injuries to walk again -- albeit "rarely and poorly," said Sefton -- are signs that tissue engineering may one day have an impact on brain and nervous-system functions.

It's not uncommon to hear the actor Christopher Reeve, who suffered a devastating spinal cord injury in a horseback riding accident several years ago, talk about walking again with regenerated spinal cells. "It's pretty impressive compared to what was there before," said Sefton. "People are working on it and making progress. Whether it needs a big breakthrough or incremental progress, it's hard to judge."

The heart has already proven itself receptive to tissue-engineering techniques, according to several recent reports.

At Charite Hospital in Berlin, Germany, doctors implanted pulmonary valves engineered from patients' own cellular material into 23 people suffering from aortic heart disease. Three years later, the valves still performed normally, according to a report presented in November at the American Heart Association conference in Orlando, Fla. The valves were created using a piece of vein from each patient's arm or leg. Cells from the vein were then cultivated on a scaffold created from a donated pulmonary valve scraped clean of cells, leaving only the collage structure to which the venous cells bound themselves.

In time, the patients' cells coated the vein. The structure is absorbed by the body in about a year, according to the doctors who conducted the study. Doctors admitted that the scaffold technique for building a new vein is still experimental.

Patients who received the tissue-engineered pulmonary valves suffered no fever post-op, a common sign of immunological rejection to a transplanted part. They were released from the hospital sooner as a result.

The scaffolding technique is being used by other scientists to engineer other organs. Linda Griffith, a scientist at the Massachusetts Institute of Technology, and a team of engineers created a silicon "liver chip" on which they plan to construct a miniature replica of the human liver. The replica will be used to create drugs to help cure diseases like hepatitis C, currently the most common disease of patients on the liver-transplant wait list. Griffith was one of the scientists behind that mouse with the ear growing from its back, and the scaffolding technique she used to build that ear -- of felt and polymer - helped engineer the first liver chip as well.

Griffith now uses 3-D printing -- a computer technique that creates a three-dimensional silica model based on a computer image of the human liver. It's the same process used to make models of airline engines.

The liver is of particular concern to those involved with the transplant process because the number of patients on the waiting list for livers has increased "dramatically" in the last 10 years, according to Miriam Perez of the Organ Donor Network in New York.

"First, hepatitis has been increasing over the years. Another reason is the intake of medication that is causing more liver damage. Thirdly, obesity plays a big factor in damaging your liver. We're obese here. Also, poor nutrition, alcoholism, drug addiction. Lack of care and not following up with your doctors -- people who were never diagnosed until they went into liver failure, they're pumping up the numbers as well," Perez said.

Though Griffith has no intention of creating a full-scale bioengineered liver, she hopes that drug trials conducted with her miniature replica will nonetheless stem the tide of those needing liver transplants.

Meanwhile, Sefton and his team will continue their mission to build a full-scale human heart. Sefton estimates that LIFE Initiative's efforts will result in the creation of an engineered human heart in about 20 years.

"If you're young, it sounds soon to you. If you're middle-aged like me, you wonder if you're going to see it through," he said.