Another milestone for custom-crafted transplants: the world’s first lab-built sphincters. The breakthrough offers hope to countless people who have become incontinent through damage to their own anal sphincters.
The spare-part sphincters were made with some human cells, but have been implanted only in mice so far. Researchers made them by growing donated smooth muscle cells from human sphincters alongside gut nerve cells from mice in circular moulds.
“The smooth muscle cells align themselves around the mould in a perfect, continuous circle,” says Khalil Bitar of Wake Forest Baptist Medical Center’s Institute for Regenerative Medicine in Winston Salem, North Carolina. Bitar led the research team while working at the University of Michigan Medical School in Ann Arbor. “The neural cells then innervate this structure and make filamentous structures and projections around it,” he says.
By testing the replacement sphincter with electric shocks and chemicals, Bitar’s team made sure that it contracts and relaxes as a normal sphincter does to keep gut contents in or let them out. More importantly, it survived and grew when implanted beneath the skin in the upper back of mice. “It rapidly gets its own supply of blood vessels, and nerves rapidly connect with the mouse’s own nervous system,” says Bitar.
Bitar is now testing the system in larger animals. The team will also have to demonstrate that the engineered sphincters can function effectively when implanted in place of existing sphincters in the anus as a prelude to trials in humans, which they hope to begin in three to five years. For those clinical trials, the plan is to obtain smooth muscle and gut nerve cells from patients themselves, then grow these into replacement sphincters for implantation. “We can custom-make them the size and diameter we want,” he says.
Bitar says that the sphincter he has made wouldn’t replace the outer anal sphincter – the one healthy people control voluntarily – but the inner one, which operates involuntarily. Current treatments include reconstruction using muscle from limbs, electrical stimulation of sacral nerves, mechanical replacements and pumps – but Bitar says these are fraught with complications and failures.
“Successful development of a bioengineered physiologic internal sphincter would represent a distinct advantage over currently available mechanical artificial sphincters,” says Robert Madoff, who researches colon and rectal surgery at the University of Minnesota Medical School in Minneapolis.
Those most likely to benefit from the new research are women who have been injured during childbirth and the elderly. Bitar says that the same technique could be adapted to make other important sphincters, such as those that hold in urine.
Journal reference: Gastroenterology, DOI: 10.1053/j.gastro.2011.03.056
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