Human Cells Engineered to Make Functional Anal Sphincters in Lab

"In essence, we have built a replacement sphincter that we hope can one day benefit human patients. This is the first bioengineered sphincter made with both muscle and nerve cells, making it 'pre-wired' for placement in the body," said senior author Khalil N. Bitar, Ph.D., a professor of regenerative medicine at Wake Forest Baptist Medical Center's Institute for Regenerative Medicine. Bitar performed the work when he was on the University of Michigan faculty and it included a colleague from Emory University.

Sphincters are ring-like muscles that maintain constriction of a body passage. There are numerous sphincters in the human body, including those that control the release of urine and feces. There are actually two sphincters at the anus -- one internal and one external. Fecal incontinence is the result of a weakened internal sphincter.

There is a high incidence of weakened internal fecal sphincters in older adults; and women who have had episiotomies during childbirth can also be affected. "Many individuals find themselves withdrawing from their social lives and attempting to hide the problem from their families, friends, and even their doctors," said Bitar. "Many people suffer without help."

Current options for repair of the internal anal sphincter include grafts of skeletal muscle, injectable silicone material or implantation of mechanical devices, all of which have high complication rates and limited success.

To engineer an internal anal sphincter in the laboratory, the researchers used a small biopsy from a human sphincter and isolated smooth muscle cells that were then multiplied in the lab. In a ring-shaped mold, these cells were layered with nerve cells isolated from mice to build the sphincter. The mold was placed in an incubator for nine days, allowing for tissue formation. The entire process took about six weeks.

Numerous laboratory tests of the engineered sphincters, including stimulating the nerve cells, showed normal tissue function, such as the ability to relax and contract. The sphincters were then implanted just under the skin of mice to determine how they would respond in the body. Mice with suppressed immune systems were selected so that there would be no issues with rejection.