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Tiny `livers' are grown in laboratory

Linda Griffith-Cima is growing miniature "livers" smaller than a dime. Or to be more precise, the little "organs" are growing themselves.

Professor Griffith-Cima 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) from rats inside a biodegradable polymer device. The device acts as a scaffold for forming the tissue. It has an "artery" at one end and a "vein" at the other. Between the two is a network of smaller, branching channels.

In a few days, the cells sort themselves and begin assembling into the patterns found in nature. The liver cells form a lining inside the channels. The blood vessel cells form a layer on top of the liver cells. Then the cells together begin forming 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 Dr. Griffith-Cima, the Karl Van Tassel Assistant Professor of Chemical Engineering. "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 self-assemble."

The immediate goal of the project, supported in part by a Whitaker Biomedical Engineering Research Grant, is to understand how liver cells grow and organize into a functional liver. The long-term 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.

Professor Griffith-Cima'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.

"There's an advantage to doing it this way that's clinically important," Professor Griffith-Cima 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."

An enabling technology for this approach to liver transplants is an innovative materials-processing technique called 3-Dimensional Printing (3DP). 3DP was developed by Michael J. Cima, Norton Professor of Ceramic Processing in the Department of Materials Science and Engineering, and Professor Emanuel M. Sachs of the Department of Mechanical Engineering. The two maintain an active collaboration with Professor Griffith-Cima.

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

"He's totally dedicated to saving kids," Professor Griffith-Cima said. "When everything seems impossible, he says, `No, it's not,' and then you go back and think of things in a different way.

"There is a big difference in the training of an engineer and a physician," she 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."

(This piece is adapted from one which originally appeared in the recently issued 1995 annual report of the Whitaker Foundation.)

A version of this article appeared in MIT Tech Talk on May 22, 1996.

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