Researchers aim to end agonizing wait for transplants

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Aug. 12, 2003 — Organ farming has always been one of the more macabre slices of science fiction: mad scientists growing livers, brains, kidneys and the like in strange tanks, awaiting transplantation into some Frankenstein creation. 

Dr. Joseph Vacanti is trying to make organ farming a reality. His work is anything but a horror show — and thanks to MEMS technology, it won’t be the stuff of fiction forever.

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Vacanti is spearheading a collaboration between Massachusetts General Hospital and nearby Draper Lab to create microscale scaffolding that coaxes cells to grow into complex tissue formations. He is one of many pursuing the much-prized, painfully elusive goal of growing cellular structures in three dimensions, just as they grow in the human body.

If he succeeds, the medical and economic payoff will be enormous: faster and cheaper drug development, improved kidney dialysis machines, and Vacanti’s ultimate dream of growing fresh tissue to end the agonizing wait for organ transplants.

“There is an overwhelming need for this,” says Vacanti, a professor of surgery at Harvard Medical School. “This is the most difficult problem in tissue engineering.”

MEMS technology is quickly proving to be the solution. Some research outfits like Vacanti’s sculpt polymer scaffolds only a few microns in size that will give cells a framework to aggregate. Others have developed self-assembling peptides to accomplish the same feat. Still another approach is to build a microscale bioreactor, essentially a container that mimics in-vivo (inside the body) conditions and can keep cells alive.

“MEMS is the only way to solve this problem,” says Jeffrey Borenstein, head of the Biomedical Engineering Lab at Draper, and Vacanti’s research partner. “With MEMS and nanotechnology, you can build the structure and put the cells right where you want them.”

Creating in-vivo conditions outside the body is extremely difficult to do. Researchers can use a petri dish to study basic cellular reactions to a drug, but that environment is two-dimensional; it cannot account for pressure, gravity and other forces at play in the living body, or accurately gauge how cells interact with each other.

That unpleasant fact has dogged the pharmaceutical industry. Drug compounds can behave as predicted in the lab, and even in animal tests — then provoke different reactions in human clinical trials. A botched human trial can cost millions, so pharmaceuticals welcome any means to conduct more accurate tests before trials begin.

Hepatometrix Inc., a startup that sprouted from MIT last year, has developed a matrix system that can deliver oxygen and nutrients to liver cells, keeping them alive for as long as 70 days. That would be ample time to test drug compounds for toxicity and to see how the liver metabolizes them, which are crucial bits of information for any new drug.

Kevin Leach, chief scientist for Hepatometrix, says the technology is already in beta tests with four major pharmaceutical firms. Pfizer Inc. has also agreed to test the matrix. “It costs pennies to do this early on, but millions of dollars if you fail in trials,” Leach says.

Leach and his six-person team hope that these early tests will win over Big Pharma and help secure funding for their other project: a bioreactor, about the size of a penny, that keeps liver cells alive and provides better means of examining the cells’ behavior at the same time. Using photon microscopy, the reactor can give clean images of the living cells.

Another MIT startup chasing the problem is 3D Matrix Inc. The brainchild of biochemistry professor Shuguang Zhang, 3D Matrix has created a system of peptides that self-assemble into strands about 50 nanometers thick. These webs provide the framework for cells to grow into complex tissue. 3D Matrix now sells the peptides as a growth medium called Puramatrix. Company President Zen Chu says the next step is to see how the peptides can work as a substitute for collagen, and possibly to help regenerate nerve cells.

Borenstein began by machining networks onto a silicon wafer and lining them with epithelial cells, which form the capillaries crucial to keeping tissue alive. (Historically, the obstacle has been that blood vessels grew too slowly, so cells at the center of a structure died.) Next he lined up two-dimensional lattices of polymers on a thin film, stacking as many as a dozen films on top of each other to form three-dimensional networks. He then lined those networks with epithelial cells and liver cells, which thrived. So far Borenstein’s lab has kept liver cells alive as long as two weeks.

As a specialist in organ transplants for children, Vacanti knows the consequences of the transplant organ shortage too well. According to the United Network of Organ Sharing, more than 82,000 people in the United States alone are waiting for transplants. Only 5,300 organs have become available this year.

Says Vacanti: “There’s an overwhelming need for this, in every area of surgery.”


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