Novel stem cell therapy for perianal fistula in pediatric patients with Crohn's disease

July 14, 2022

A new treatment for perianal fistulas in pediatric patients with Crohn's disease is under development at Mayo Clinic Children's Center.

Crohn's disease is a type of inflammatory bowel disease (IBD) that is most common in individuals ages 15 to 35, but the frequency of pediatric onset is increasing. Common symptoms in children include cramping and abdominal pain, chronic episodes of watery diarrhea, and blood in the stool. Symptoms may also include fever, fatigue, nausea and loss of appetite. Malnutrition due to malabsorption, poor growth, and low weight gain and anemia also may occur.

Crohn's disease may lead to a gastrointestinal fistula, an abnormal connection between the bowel and adjacent structures such as the bladder, vagina, fallopian tubes, skin or other areas of the bowel.

Patients with Crohn's disease most often develop fistulas in the perianal area, which may result in infection, fecal incontinence, perianal discharge and significant psychosocial challenges. Treatment and repair can involve multiple surgeries and have a profound impact on quality of life. Pediatric onset of Crohn's disease is associated with more-aggressive perianal fistula development.

There are various surgical options that may encourage fistula closure. One option is a seton, in which a length of surgical thread is looped through the tract of the fistula and out the anal opening. This creates chronic inflammation that can help encourage healing and closure while preventing infection. However, not all patients experience full resolution of their fistulas with this technique. The procedure can be painful for the patient as well.

Approximately 15% of children do not respond to medical treatments for fistula and require additional intervention, according to Michael C. Stephens, M.D., a pediatric gastroenterologist at Mayo Clinic Children's Center who specializes in pediatric inflammatory bowel disease at Mayo's campus in Rochester, Minnesota. "Perianal fistulas can be a source of significant pain for children and have a very detrimental effect on self-esteem. Finding help for those who don't respond to medical therapies can have a tremendous impact on quality of life," says Dr. Stephens.

Michelle M. Gonzalez, M.D., a pediatric gastroenterologist with expertise in pediatric inflammatory bowel disease at Mayo Clinic in Rochester, Minnesota, is researching the applications of a new type of stem cell therapy to help treat fistula in patients who do not respond to first line therapies. Dr. Gonzalez says, "The benefit of being a patient at Mayo Clinic is the active collaboration between different groups of leading experts in the field, including those of the adult IBD practice."

Dr. Gonzalez and her research collaboration have expanded on a study completed in adults by William A. Faubion Jr., M.D., director of the pediatric inflammatory bowel disease clinic at Mayo Clinic in Rochester, Minnesota, and other Mayo clinicians. Treatment uses stem cells derived from a patient's own fat cells to create a plug. The plug is inserted into the fistula tract to close the fistula opening.

A phase 1 clinical trial at Mayo Clinic involving 12 adults used autologous mesenchymal stem cells (MSCs) applied in a bioabsorbable matrix. After six months, 10 of the 12 participants had full clinical healing and radiographic markers of response without any serious adverse events.

This technology has been adapted for use in pediatric patients at Mayo Clinic Children's Center with positive initial results. A current study seeks to help children who do not respond to medical therapy for their fistulas.

Specialized cells called MSCs are extracted from a sample of fat collected from under the skin of the patient and grown in a research laboratory. MSCs have unique properties that allow them to accelerate healing in tissue that is damaged. The cells are allowed to grow with a specialized plug that is very porous and fibrous so that the cells can permeate and coat the material. Once the plug is completely encapsulated with the stem cells, a surgeon can position it through the fistula tract.

Dr. Stephens is optimistic about this study. "Because we use the patients' own cells to envelope the plug that fills the fistula, we think it will be much more likely to achieve effective healing and an outcome that is much closer to what the patient experienced before the onset of Crohn's disease," he explains.

Stem cell plugs may provide an alternative treatment option for children who do not respond to medical therapies without the need for multiple surgical interventions, thereby reducing medical costs and burden on the patient.

For more information

Mayo Clinic Children's Center.

Dietz AB, et al. Autologous mesenchymal stem cells, applied in a bioabsorbable matrix, for treatment of perianal fistulas in patients with Crohn's disease. Gastroenterology. 2017;153:59.

Mayo Clinic. Pediatric MSC-AFP Sub-study for Crohn's Fistula.

Refer a patient to Mayo Clinic.