Anthony Atala

PROFILE Anthony Atala becomes fibrotic. Atala’s scaffolds, of collagen and polyglycolic acid, last A single-minded focus on bringing scientific advances to patients for a few months until the bladders can survive without them. has driven Anthony Atala’s pioneering work in tissue engineering. But perhaps the most formidable problem was simply creating an organ as large and thick as a bladder, which requires extensive vascularization. In vitro–engineered tissues cannot generally be grown thicker Turning tissue-engineering research into biotech products is no easy task. than about 300 µm because the cells at the center lack nutrients and But Anthony Atala, director of the Wake Forest Institute for Regenerative oxygen. Atala’s solution was to enlist the body as a “terminal incubator”: Medicine, is intent on finding a way. In a recent landmark paper, his although the scaffold is formed and seeded with cells on a benchtop, group reported the first human trial of tissue-engineered bladders1. most organ growth takes place in the body, where vascularization occurs Transplantation of the artificial organs in seven young spina-bifida patients spontaneously. As Atala notes, however, this method of vascularization proved just as safe as the gold-standard treatment—surgical reconstruc- is limited to hollow organs and would not apply to solid organs like the tion using intestinal tissue—and avoided its debilitating complications. heart and liver. “The work has tremendous potential clinical benefits,” says David Atala’s clinical trial is only a first step towards made-to-order bladders. Joseph, chief of pediatric urology at the University of Alabama School of Further progress will involve refining the fabrication method, studying Medicine in Birmingham. Alan Russell, director of Pittsburgh’s McGowan more patients and examining more endpoints. Joseph cautions that Institute for Regenerative Medicine, describes it as “the first example of because of the children’s underlying disease, the bladders lack proper a large, complex, ‘thin’ organ being regenerated in humans.” In the wake innervation and do not void, requiring long-term catheterization. But of Atala’s work on hollow organs, solid organs represent the next major the organs may function normally in other situations, he says. “Tony’s challenge for tissue engineering. approach opens up new avenues for people who have lost all or part of Trained as a pediatric urological surgeon, Atala became interested in their bladder from a tumor, for example.” Tengion, a biotech company thehttp://www.nature.com/naturebiotechnology potential of tissue engineering to improve surgical outcomes and address shortages of donor organs during a 1990–1992 fellowship under Alan Retik at Children’s Hospital Boston and Harvard Medical School. He remained there as a faculty member, dividing his time between surgery “In tissue and research, until January 2004, when he took up his new post at Wake engineering,” Forest University in Winston-Salem, North Carolina. The bladder is just one of many organs he has sought to regenerate; others include skin, Atala says, urethras, blood vessels, cartilage, cardiac and skeletal muscle, vaginas, “everything goes uteri, bone, kidneys and tracheas. “In tissue engineering,” Atala says, “everything goes back to scar for- back to scar mation.” Group Nature Publishing Scarring, also known as fibrosis, underlies how tissues fail in 6 formation.” disease—and how they are regenerated. In normal wound-healing, the body200 recruits collagen, fibroblast cells, bone marrow cells and cells from the© wound’s periphery, a recipe that is not sufficient to prevent a scar. Will Willner/ WFUSM Atala wondered what other ingredients would be needed to grow a tissue from scratch. Simply adding certain scaffold materials to a wound, he found, lessens the scar. And including tissue-specific progenitor cells in King of Prussia, Pennsylvania, intends to take Atala’s work forward in reduces it even more. phase 2 and 3 trials. Whatever the tissue he wants to generate, Atala searches for felicitous Meanwhile, Atala himself has turned his attention to engineering other combinations of scaffolds and cells. The bladders, for example, are made organs with the help of his new institute at Wake Forest. In Boston he by expanding urothelial and muscle progenitor cells from a patient biopsy had grown weary of the turf wars that can slow the translation of tis- and seeding the cells onto a bladder-shaped scaffold. After a few days sue-engineering research to the clinic, an effort that depends on multi- in culture, the proto-bladder is overlaid with fibrin glue (for structural disciplinary collaborations and broad institutional support. Thus, when stability) and omental tissue (to provide a vascular bed) and promptly he was approached in 2003 by Richard Dean, president of Wake Forest transplanted into the patient. Three months later the bladder is two- University Health Sciences, to head a regenerative medicine institute of thirds grown; at six months it is similar to a normal bladder and the his own, he jumped at the chance. scaffold is fully degraded. “The institute is an experiment,” Atala says. “Unlike some tissue- Since 1990, when he began the project, Atala has studied artificial blad- engineering centers, it’s not virtual.” Faculty members hold primary ders in four animal models, overcoming critical obstacles along the way. appointments at the institute rather than in a department, creating a The first hurdle was simply getting the urothelial cells to survive and strong culture of teamwork. “The structure of the institute does away proliferate. For three years he tested countless culture conditions without with politics, with dual loyalties of the faculty. In a traditional institute, success. Then one day the surgical bladder specimens arrived hours late, one is often faced with conflicts—who sends out the grant, and so on. so he skipped the collagenase treatment used to dissociate the cells and Here, no one is fighting over grants and publications.” As a result, he says, simply scraped the cells from the specimens manually. Two days later, the institute’s scientists can focus on what is most important: “bringing the cells were proliferating. technologies to patients, effecting changes in people’s lives.” Another challenge was finding a good scaffold material. If the scaffold Kathy Aschheim, San Francisco degrades too quickly, the bladder collapses; too slowly and the bladder 1. Atala, A. et al. Lancet 367, 1241–1246 (2006). NATURE BIOTECHNOLOGY VOLUME 24 NUMBER 11 NOVEMBER 2006 1311.

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