MIZZOU NEWS

Creating ‘Natural’ Human Organs

By Matt McGowan

Gabor Forgacs’ work with organ engineering is an excellent example of how current interdisciplinary research in the life sciences may have a profound impact on future generations. Forgacs, a biological physicist at the University of Missouri-Columbia, is an integral part of a research team that ultimately plans to build organs in laboratories for the purpose of human transplantation.

“Before we can realize this ambitious goal, however, we must start at the foundation,” Forgacs said. “To function properly, organs need blood. Our aim now is to build vasculature, tissue that can deliver blood.”

Already, Forgacs has made critical steps in pursuing this immediate goal. In his lab at MU, he and several researchers, including medical doctors, cell and developmental biologists, and computer and biological engineers, have laid down the cellular, biophysical and bioengineering foundations for creating tubular organs similar to blood vessels. Most importantly, Forgacs’ MU research team is the first to have demonstrated that spherical cell aggregates — thousands of cells combined to form a ball — can be made and manipulated, and that under appropriate conditions these aggregates will fuse to form vessel-like structures.

Forgacs relied on his knowledge of the laws of physics to predict what would happen if different cell types were combined. First, he knew that embryonic tissues share properties with liquids. Forgacs then thought about how liquids behave based on their inherent physical properties. Because they seek to minimize their surface area, liquid drops “round up.” In other words, under the right conditions the molecules in a drop of liquid move around until the drop acquires a spherical shape. Forgacs also knew that one type of liquid can engulf another type. For example, oil engulfs water.

These physical principles helped Forgacs predict that when different types of cells were mixed together, they would adhere, eventually forming a spherical aggregate, and would arrange in the “right” physiological order. This understanding was critical because human organs typically consist of different types of cells.

Forgacs also knew that different cells have their own distinct adhesion apparatuses. Using computer modeling, his team predicted that if the cell aggregates were arranged in a circular pattern in the appropriate biocompatible gel, they would fuse together to form a ring or tube. Forgacs and his researchers tested the prediction by first manually arranging the aggregates in a circular pattern. Over a 24 hour period, the aggregates fused and created a thick ring, a vessel-like organ. The physical arrangement of aggregates using a modified commercially available ink-jet printer — “organ-printer” — is now under way.

Forgacs plans to refine the experiments on the basis of the models constructed by his team. They are presently stacking several circular layers of aggregates onto gelatinous tissue to cause the layers to fuse into tubular structures.

In addition to the long-term goal of producing vascular tissue for building human organs, researchers hope to produce tissue that will serve as grafts in surgeries to repair arteries and veins. Forgacs cautions that science is many years away from creating a “natural” human organ, but the ability to build blood vessels is an important scientific advancement.

Organ and tissue engineering is a relatively new but thriving area of research in the life sciences. Previous research has focused on creating tissue that does not require blood for sustenance. Researchers have had success building cartilage and ligaments to insert into deteriorated skeletal joints.

Some of the research team’s results will soon be published in Trends in Biotechnology. In addition, Forgacs will present his findings in March at an international conference on tissue engineering. The National Institutes of Health solicited the team to submit a grant application, which it has done.

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Last Update: March 12, 2007