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Organs built in the laboratory might someday eliminate transplant waiting lists. Already, surgeons are transplanting blood vessels, urethras and bladders constructed from patients' own cells, eliminating the risk of rejection.
A medical team in Mexico, for instance, successfully transplanted engineered urethras into five young boys. To hold their shape, natural organs have an underlying “scaffold” made of proteins. The Mexican team built their scaffolds from scratch, out of biodegradable polymers and natural molecules such as collagen. The doctors then seeded the scaffolds with epithelial cells and smooth muscle cells retrieved from each child. It took four to seven weeks for the urethras to grow and be ready for transplant.
Researcher Daniel Eberli of the Institute for Regenerative Medicine at Wake Forest University School of Medicine in Winston-Salem, N.C., “seeds” human bladder cells onto a specially constructed biodegradable mold, shaped like a bladder. Surgeons are transplanting blood vessels, urethras and bladders constructed from patients' cells, eliminating the risk of rejection and helping to shorten transplant waiting lists. (AP Photo/Brian Walker)
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But urethras, blood vessels and bladders are relatively simple organs. An intestine, on the other hand, is more complex, with a variety of types of cells that absorb water, sodium, sugars and proteins, support bacteria and house a sophisticated immune system.
Tracy Grikscheit, a pediatric surgeon at Children's Hospital Los Angeles, cares for premature infants with short bowel syndrome, which makes it difficult for them to absorb nutrition. They're fed intravenously, which can cause infections, blood clots and, potentially, cirrhosis of the liver, often making an intestine transplant inevitable.
However, the intestine's robust immune system makes it particularly prone to rejection. “Transplant outcomes are not great,” says Grikscheit. The five-year survival rate of a grafted intestine is less than 50 percent.
So Grikscheit and colleagues experimented with pigs. They built a biodegradable cylindrical scaffold and seeded it with epithelial cells from a pig's intestine. They then incubated the structure on top of blood-rich tissue inside the pig's abdomen. When removed seven weeks later and placed under the microscope, it looked just like a small intestine. It's not yet clear whether it would function if actually transplanted into the pig, but Grikscheit is optimistic and believes the research will eventually translate to humans. “I hope to do this in humans within five to 10 years,” she says.
Lungs, kidneys and hearts are even more of a challenge. But scientists are making progress. Researchers from Yale University, for example, have created functioning rats' lungs. They did not build the scaffolds from scratch, however. “It's simply too difficult to try and make such a complex, three-dimensional scaffold,” says Thomas Petersen, a post-doctorate associate at Yale. Instead, he and colleagues dissolved the cells from adult rat lungs, leaving behind the scaffolds, which the researchers then seeded with epithelial cells from baby rats.
Petersen says researchers really don't understand how the scaffolds directed the epithelial cells to turn into the variety of cells that line the lung. But somehow they did, and the team transplanted the engineered lungs into four live rats, where they functioned at 95 percent of normal capacity for two hours. After that, small leaks and blood loss developed.
If the technique were ever to be used in humans, the scaffolds could come from human lungs that are not currently suitable for transplant, or even from another species, and be seeded with each patient's own cells, making lung shortages and rejection things of the past. But it won't be happening soon.
“I think we are at least 20 years or more from human use,” says Petersen.
— Barbara Mantel
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