MIT's Griffith-Cima Engineers "Spare Parts"

NEW YORK-­Linda Griffith-Cima, the Karl Van Tassel Assistant Professor of Chemical Engineering at the Massachusetts Institute of Technology (MIT), is growing miniature "livers," which are smaller than a dime. Actually, the livers are growing themselves.

Griffith­Cima and her colleagues at MIT and Harvard Medical School place a few droplets containing a mixture of liver cells (hepatocytes) and blood vessel cells (endothelial cells) inside a biodegradable polymer device, which acts as a scaffold to form the tissue, and has an "artery" at one end and a "vein" at the other. In the middle is a network of smaller, branching channels.

Within a few days, the cells sort themselves and begin assembling into natural patterns. Liver cells form a lining inside the channels; blood vessel cells form a layer on top of the liver cells. Then, the cells together form pillars that bridge one side of the channel wall with the opposite wall.

"The cells are trying to do what they normally do: form what are called sinusoidal structures," said Griffith­Cima. "There is a scale at which we see these structures. If the diameter of the channel is too small or too large, it doesn't happen. One of the things we are studying is the scale at which these cells self­assemble."

The project's immediate goal is to understand how liver cells grow and organize into a functional liver. Its long­term goal is to cultivate replacement organs for the 30,000 Americans who die annually from liver failure. Fewer than 3,000 livers become available each year for transplant, and there is no widely used assist device like the dialysis machine for kidney patients. Transplantation is the only hope for patients with liver failure.

The liver, the largest of the internal organs, has powerful regenerative properties, like the spire of a starfish or the tail of a chameleon. Cut a liver in half and, within six weeks or so, it will restore itself.

Griffith­Cima's group envisions growing enough liver cells to form a small organ, then implanting the small liver in the portal vein that leads from the digestive system to the liver. The scaffold supporting the cells would dissolve in the same way that internal resorbable sutures do, leaving behind a miniature liver.

Engineering achievements, like Griffith­Cima's are celebrated each year during National Engineers Week, held this year from February 22-28, 1998.

"There's an advantage to doing it this way that's clinically important," Griffith­Cima said. "Right now, about 15 percent of all liver transplants do not take hold. That means that in a day or two, another donor has to be found. Our approach would enable a surgeon to implant a functioning liver without taking out the old organ. That might be enough to restore normal function. We don't want to take the old liver out until we are sure the new one is functioning properly."

Griffith­Cima's key clinical collaborator is Joseph Vacanti, a Harvard Medical School surgery professor and head of transplant surgery at Children's Hospital in Boston, who originated the idea of growing the tiny livers.

"There is a big difference in the training of an engineer and a physician," Griffith­Cima said. "I'm trained as a chemical engineer. For years, the main thing chemical engineers did was design chemical plants and oil refineries. And, you had to build in a 'fudge factor,' so that if something failed, it would still work perfectly because of the backup. But, when you're working in medicine, you don't wait until something is perfect. You'll never get anything done. If something has a chance of saving a life, you build it the best way you can now and improve it later."

Griffith­Cima came to national attention in 1995 for her tissue engineering work in developing replacement human ears, grown on the back of a mouse. Her research involved creating a mold in the shape of a human ear, distributing human cartilage cells throughout the form, and implanting the prototype ear on the back of a hairless mouse.

The specially bred mouse, which lacks an immune system, nourishes the cells as they grow, and when the ear­shaped cartilage is harvested, the mouse remains alive and healthy.

Griffith­Cima said she began growing "mouse ears" to assist a friend, who's a plastic surgeon.

National Engineers Week, celebrated February 22-28, 1998, celebrates the achievements of engineers­like Griffith­Cima­who have made a difference in our health and healing.

Founded in 1951 by the National Society of Professional Engineers, National Engineers Week is sponsored by 15 major corporations and 18 engineering societies, including the American Institute of Chemical Engineers, with the cooperation of hundreds of businesses, colleges, professional and technical societies, and government agencies. Its goal is to promote public understanding and appreciation of engineering and technology. The event is held the third week of February each year in honor of George Washington's Birthday, who is considered to be the nation's first engineer.

# # #

National Engineers Week Foundation
1420 King Street   Alexandria, VA 22314
tel. 703.684.2852   email: eweek@nspe.org