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Tissue engineering takes a leap forward with new scaffold design

Yale Medicine Magazine, 2006 - Autumn


Tissue engineering began in the late 1980s to fill a gap in the treatment of certain diseases—those for which transplants could offer a cure. There isn’t enough natural human restorative tissue to go around, however, and two recent studies at Yale show how clinical applications of tissue engineering are coming within reach.

In one study, researchers created a tiny water-soluble “scaffold” that provides a framework for the growth of new blood vessels; in the other, they demonstrated that the technique for creating new arteries—manipulating telomerase to extend cell life—doesn’t necessarily cause cancer, as had been feared. Both papers appeared in the February 21 issue of the Proceedings of the National Academy of Sciences.

“A microvascular network is fundamentally important for tissue engineering,” said Erin Lavik, Sc.D., an assistant professor of biomedical engineering and author of one of the studies. She added, however, that the “stability of microvascular networks has been a challenge.”

Lavik’s team built scaffolds out of gelatin-like, porous hydrogels that can be chemically treated to form numerous interconnected internal pores. In collaboration with Joseph A. Madri, M.D., HS ’76, Ph.D., professor of pathology and of molecular, cellular and developmental biology, Lavik and her colleagues seeded the gels with blood vessel cells, implanted them under the skin of mice and found that functional and stable vessel networks had formed after six weeks.

Scientists have been able to create new arteries in humans by using the patient’s own cells, but one drawback has been that these replacements haven’t been as effective in older people. A second Yale team found a way around that problem last year.

Researchers had previously used gene therapy to deliver telomerase, an enzyme that extends the cells’ normal life span by lengthening their chromosomes following cell division. The technique worked, even in patients as old as 85, said Laura E. Niklason, M.D., Ph.D., an associate professor of anesthesiology and biomedical engineering. Telomerase, however, is highly active in cancerous cells. “One of the outstanding questions is, ‘How safe is this?’,” she said.

In the latest study, which involved tissue samples from eight elderly patients and one young donor, Niklason’s team took cells obtained during a coronary bypass procedure and increased telomerase expression. They discovered that they had not produced cancerous cells in so doing. “Just turning on telomerase by itself is not enough to create cancer,” she said.

Although Niklason said more work is needed, her findings may one day enable the development of techniques for making replacement tissue.