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Body Shop: Need Some Vessels for Your Liver

Anna Liachenko, MSc
Managing Editor
Geriatrics & Aging

Despite the recent progress with transgenic pigs and tissue engineering, we are still in serious need of both functional and immuno-compatible organs, especially such complex organs as the liver, kidney and heart. Until recently, the artificial creation of complex organs seemed an unobtainable goal, mostly due to the challenge of providing them with proper vascular support. Recently, Joseph Vacanti and his colleagues created an artificial vascular system--a 'circulatory-system-on-a-chip'--that may soon solve the problem.

In organ engineering, living cells are first grown in the lab on scaffolds of biodegradable plastic, where they spontaneously arrange into functional tissues. Once the plastic template is degraded and the newly formed organ is implanted, the body's vascular system grows in. This approach has made available lab-grown replacements of both skin and cartilage, but has not yet been successful for the development of a more complex organ. The challenge is that the body's blood vessels do not grow fast enough to sustain thick tissues, and the inside part of the artificial organ dies before it can obtain the nutrients and oxygen necessary for its continued survival.

Vacanti's group proposed a solution to this problem by making an artificial vascular network, which will then be combined with other artificially grown tissues, to yield a complete organ. Early attempts at mimicking vascular support for the lung and liver revealed two problems: poor blood flow, and a shortage of the capillaries that are so necessary to ensure adequate nutrition for the tissue. The system is being re-designed to deliver blood at pressures at which it would normally be received by the given organ, and by quadrupling the number of capillaries. When this phase is complete, the researchers will tackle the issue of converting the paper-thin, vascular sheets into complete organs. The task is challenging given that several hundred square feet of vascular tissue, or about 7,000 of the 4-inch wafers, are needed to match the blood-cleansing power of an adult liver. These will have to be merged into a 3-D network complete with hepatocytes and fibroblasts. Three main approaches have been proposed--'stack", "jelly roll", and 3-D scaffolds. In the "stack" approach, sheets with various cell types are alternated and stacked on top of each other. In the "jelly roll", sheets are laid side by side and are then rolled together. In 3-D scaffolds, a biodegradable polymer guides the growth of the blood vessels. All three approaches will be investigated with respect to their ability to provide blood to the organ tissues.

While Vacanti's group is currently the closest to creating vascular support for artificial organs, Michael Sefton, a tissue engineer at the University of Toronto, is investigating other options. "Our goal is similar to that of Joseph Vacanti, except that our approach is based on exploring the principles of angiogenesis, which is a natural process of growing blood vessels, by adding growth factors or other factors," he says. Sefton & Vacanti are currently collaborating on a project called the 'Life Initiative,' which is a 'multi-institutional and multi-national project to grow large organs.

Just think, in a couple of years you may be able to get an artificial liver or heart via the Internet!