Researchers here report on progress in engineering a few parts of the digestive system. The intestine and sphincter work here goes together with advances in the production of small sections of functional stomach tissue reported earlier this year. The field is doing well, considering that the challenge of generating the blood vessel networks necessary to support larger tissue masses has not yet been resolved. Researchers are finding a fair number of areas where they can proceed to potentially produce useful therapeutic outcomes even absent that capability.
Researchers have reached important milestones in their quest to engineer replacement tissue in the lab to treat digestive system conditions. They have verified the effectiveness of lab-grown anal sphincters to treat a large animal model for fecal incontinence, an important step before advancing to studies in humans, and also achieved success in implanting human-engineered intestines in rodents. The lab-engineered sphincters are designed to treat passive incontinence, the involuntary discharge of stool due to a weakened ring-like muscle known as the internal anal sphincter. The muscle can lose function due to age or can be damaged during child birth and certain types of surgery, such as cancer. Current options to repair 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.
The team has been working to engineer replacement sphincters for more than 10 years. In 2011, the team was the first to report functional, lab-grown anal sphincters bioengineered from human cells that were implanted in immune-suppressed rodents. The current study involved 20 rabbits with fecal incontinence. The sphincters were engineered using small biopsies from the animals’ sphincter and intestinal tissue. From this tissue, smooth muscle and nerve cells were isolated and then multiplied in the lab. In a ring-shaped mold, the two types of cells were layered to build the sphincter. The entire process took about four to six weeks. In the animals receiving the sphincters, fecal continence was restored throughout a three month follow-up period, compared to the other groups, which did not improve. Measurements of sphincter pressure and tone showed that the sphincters were viable and functional and maintained both the muscle and nerve components. Currently, longer follow up of the implanted sphincters is close to completion with good results.
The intestine project is aimed at helping patients with intestinal failure, which is when the small intestine malfunctions or is too short to digest food and absorb nutrients essential to health. Intestinal transplant is an option, but donor tissue is in short supply and the procedure has high mortality rates. “A major challenge in building replacement intestine tissue in the lab is that it is the combination of smooth muscle and nerve cells in gut tissue that moves digested food material through the gastrointestinal tract.” Through much trial and effort, the team has learned to use the two cell types to create “sheets” of muscle pre-wired with nerves. The sheets are then wrapped around tubular molds made of chitosan.
In the current study, the tubular structures were implanted in rats in two phases. In phase one, the tubes were implanted in the omentum, which is fatty tissue in the lower abdomen, for four weeks. Rich in oxygen, this tissue promoted the formation of blood vessels to the tubes. During this phase, the muscle cells began releasing materials that would eventually replace the scaffold as it degraded. For phase two, the bioengineered tubular intestines were connected to the animals’ intestines, similar to an intestine transplant. During this six-week phase, the tubes developed a cellular lining as the body’s epithelial cells migrated to the area. The rats gained weight and studies showed that the replacement intestine was healthy in color and contained digested food.