Boston team grows blood vessels in quest for organs

By Gareth Cook, Boston Globe Staff, 6/20/2002

A team of Boston scientists has built a living web of tiny blood vessels - a crucial advance in the long quest to grow replacement organs for humans from scratch.

Every year, thousands of Americans die waiting for an organ transplant. To meet the demand, researchers - many of them in the Boston area - have been trying to grow hearts, lungs, and other organs in the laboratory. But they have been stymied: As the new organ tissue flourishes and grows thicker, the cells are starved of blood and die.

The Boston team, which includes researchers from Massachusetts Institute of Technology and Massachusetts General Hospital, has been working to grow a new circulatory system to feed the organs. They created a vast network of tiny plastic tubes - many smaller than a human hair - and then coaxed cells to line the insides and form a network of live capillaries. The plastic tubes are designed to dissolve in the body, leaving the capillaries to supply oxygen and nutrients deep into any tissue, sustaining it.

As news of the team's progress has spread, other scientists have let out a "cheer of good will," said Michael Sefton, director of the Institute of Biomaterials and Biomedical Engineering at the University of Toronto. "This is central enabling technology for tissue engineering."

To create a liver, for example, the team hopes to alternate thin layers of capillary networks with thin layers of liver cells. When the scaffold melts away, patients would be left with a functioning mass of liver cells fed by its own blood supply.

Recently, the team has had several successes, including an experiment that showed the capillaries could handle blood flow from a living rat for hours without problems. Just last week, they were able to stack six capillary layers and the network still worked well.

"If you can stack several of them, you should be able to stack a thousand," said Joseph P. Vacanti, a pediatric transplant surgeon at Mass. General, who leads the team. The new technology, Vacanti emphasized, is still years from helping patients, and must pass several important milestones before he would even suggest testing it in humans.

The latest results have not yet been published in a scientific journal, and the team has yet to implant the capillaries into an animal to show they can keep tissue alive. But Vacanti, who has watched children die waiting for a donor, said the work has left him hopeful that the days of organ shortages are numbered.

The new blood vessels are the product of an unusual collaboration that coordinates the work of doctors, chemists, physicists, and engineers in a local organization founded in 1994, the Center for Integration of Medicine and Innovative Technology. This project, for example, is headed by a surgeon but relies on advanced fabrication technology used to etch circuits into a computer microchip.

"This would not be possible without a team that came together across disciplines," said Jeffrey T. Borenstein, a physicist at Draper Laboratory who builds the tiny tubes where the capillaries grow. "This is the best project I have ever worked on."

Scientists trying to grow new human tissue face a daunting problem. To survive, every cell in the body must be supplied with oxygen and nutrients. In nature, the problem is solved by a network of arteries, veins, and capillaries, dizzying in their complexity, which fan out across the body, splitting over and over until they are invisible to the naked eye.

"All of us are just like plants," said Vacanti. "We are based on a branching architecture."

MIT scientist Mohammad R. Kaazempur-Mofrad has been working with the team to devise a structure that branches like real capillaries. He created a computer model that predicts how blood will flow through a network, and how well it will deliver oxygen and other nutrients to the surrounding tissue. The latest versions of the network flow just as the model says they should, he said.

The team's artificial blood vessels began as a pattern of ridges on a silicon chip, etched with the same technique used to make computer chips, Borenstein said. Onto the chip was poured a thin layer of biodegradable material, yielding valleys in the pattern etched on the chip. The valleys were then sealed with another thin piece of biodegradable material, creating a system of tubes.

The researchers then injected these tubes with a steady flow of a nutrient-rich liquid, along with the cells that make up blood vessels in a rat. Within two weeks, the cells had grown to line the inside of the tubes, and the team was able to circulate blood from a rat through the network for several hours without trouble - a crucial finding, said David Mooney, a bioengineer at the University of Michigan who also works on engineering blood vessels.

Mooney called the work "a big step forward," and predicted the technology would eventually be combined with other approaches to bring blood to engineered organs, a sentiment echoed by others in the field.

The next step for the Vacanti team will be to show that their capillary networks can support other cells, such as liver cells. The team is said to be making progress in this area, but declined to provide specifics.

Next they will attempt to show that they can place working tissue in an animal. Then they hope to move to humans. "The stakes are so high, because of the number of people who could benefit from the research," said Borenstein.

"It is a long road, but every day counts."