Engineered organs may soon become a medical reality.
In the world of tissue engineering, a promising approach is underway: growing a patient's stem cells in labs, adding them to a scaffold material, and potentially offering a laboratory-grown organ. But it's been a slow journey for many, especially those suffering from severe gastrointestinal issues. Could that change soon?
Lab breakthroughs often bring new treatments to light. Yet, the path from the laboratory to a viable clinical option is long and arduous. For instance, those with short bowel syndrome or fecal incontinence — common complications affecting thousands— deserve better treatment options.
Short bowel syndrome impacts approximately 25 in 100,000 newborns yearly in the U.S., leaving them with lifelong issues. It can also occur due to cancer or other diseases. Fecal incontinence, experienced by as many as 26% of women after vaginal birth, can result from damage to the anal sphincter during childbirth, cancer surgery, or old age.
To tackle these issues, researchers from the Wake Forest Institute for Regenerative Medicine have been developing novel therapies for both anal sphincter injuries and short bowel syndrome. Yet, one burning question remains: will these life-changing therapies reach those in desperate need any time soon?
Lab-grown guts
Khalil N. Bitar,Ph.D, a professor of regenerative medicine, explains the team's strategy, saying, "We aim to use a patient's own cells to engineer replacement tissue in the lab for devastating conditions affecting the digestive tract."
The small intestine, a complex tissue, consists of muscle cells crucial for food movement, and nerves that stimulate these muscles. However, aligning these cells perfectly and co-ordinating their functions are significant challenges in tissue engineering, as cells often grow in isolation in labs.
Dr. Bitar's team has spent years developing a precise method to grow muscle cells aligned in one direction, which later connect with nerve cells. In a recent paper in "Tissue Engineering Part C: Methods," the researchers transferred sheets of both cell types onto small tubular structures, replicating the small intestine's structure.
Implanted into the lower abdomen of rats for 4 weeks, the tubes allowed blood vessels to infiltrate, then attached to the small intestine of the rats for another 6 weeks. After this period, epithelial cells — essential for nutrient absorption— were discovered migrating into the tube, and active digestion was observed.
"Engineered human intestine could provide a viable treatment to lengthen the gut for patients with gastrointestinal disorders, or for those who lose parts of their intestines due to cancer," shares Dr. Bitar.
The team plans to test the tubes in larger animal models. Meanwhile, their latest research, published in "Stem Cells Translational Medicine," demonstrates the feasibility of using an engineered anal sphincter in a large animal model to restore fecal continence.
Stem Cell Solutions
Tracy Grikscheit, M.D, an associate professor of surgery, and research investigator at the Saban Research Institute at Children's Hospital Los Angeles, employs a unique approach, adding a mixture of cells taken from the intestine to a tubular scaffold structure, including epithelial cells.
While her method yields good epithelial cell coverage and improved intestinal function in both animal and miniature pig models, muscle and nerve cells do not align as they do in native tissue.
James Dunn, M.D., a professor of surgery and bioengineering at the Stanford School of Medicine, focuses on rapidly expanding intestinal stem cells, with the long-term aim of producing cells to treat various intestinal issues.
Finally, Levilester Salcedo, M.D., and Massarat Zutshi, M.D, of the Department of Colorectal Surgery at the Cleveland Clinic, Ohio, showed improved anal sphincter function after removing 25 percent of the sphincter in a rat model with bone marrow stem cell injections.
As researchers continue to make headway in tissue engineering of the gastrointestinal tract, the question remains: how close are we to turning these promising findings into life-changing therapies for patients in need?
The Future's Calling
When asked about the biggest challenge in bringing tissue-engineered intestine to patients, Dr. Dunn pointed to the need to ensure all cell types work together harmoniously, followed by scaling the tissue-engineered intestine to clinically useful dimensions.
scaling is a common issue in many areas of tissue engineering. While therapies may work well in small rodents, enlarging them for human use is significantly more complex.
Dr. Bitar revealed that their plan for the small intestine graft is to test its effectiveness in large animal studies — a costly endeavor. Funding for scientific research, particularly the National Institutes of Health (NIH) budget, remains uncertain, so bringing these treatments to market will depend heavily on adequate funding.
Regardless, patients need pioneering scientists to keep searching for novel treatments. And as research funding remains vital, the future of tissue-engineered bowel and anal sphincter therapies may just be taking a step closer to reality.
- The Wake Forest Institute for Regenerative Medicine is developing novel therapies for both short bowel syndrome and fecal incontinence, using a patient's own cells toengineer replacement tissue in the lab.
- The team's approach involves growing muscle cells aligned in one direction and connecting them with nerve cells to form a tubular structure that mimics the small intestine's structure. This engineered intestine could potentially provide a viable treatment for patients with gastrointestinal disorders or those who have lost parts of their intestines due to cancer.
- However, scaling the tissue-engineered intestine to clinically useful dimensions remains a significant challenge. Funding for scientific research, particularly the National Institutes of Health (NIH) budget, remains uncertain, so bringing these treatments to market will depend heavily on adequate funding.
