AURORA, COLO. – Perianal Crohn’s disease with fistula is notoriously difficult to treat and can make patients’ lives miserable, but a new, minimally invasive approach involving local injection of mesenchymal stem cells is both safe and, in a significant proportion of patients, highly effective, according to a colorectal surgeon.
“It’s a really debilitating phenotype, a spectrum of phenotypes,” Amy Lightner, MD, of the Cleveland Clinic said at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
Although some patients have minimal symptoms, others may require multiple setons to aid in drainage and healing, while others may require fistulotomy, endorectal advancement flap, intersphincteric fistula tract (LIFT) procedure, diversion, or proctectomy.
Dr. Amy Lightner
“Why is it so difficult to treat? Well, part of it is that this is an anatomic defect, and this is why 90% of patients will come to the operating room and will see their surgeons on a frequent basis. The other part of that is that we have medical therapies to treat these fistulas but they’re really largely ineffective, because there is that anatomical defect, the hole there that needs to be closed,” Dr. Lightner said.
Up to 20% of patients may require a permanent stoma, and an additional 20% may require temporary fecal diversion.
Mesenchymal stem cells (MSC) are derived from bone marrow, fat stores, or umbilical cord tissues. Unlike embryonic stem cells, which have the ability to metamorphose into a multitude of other cell types, mesenchymal stem cells are differentiated “adult” cells.
They work by secreting anti-inflammatory cytokines and recruiting immune cells to stimulate tissue repair and healing. The cells are delivered in a minimally invasive outpatient setting, and there is no risk of incontinence compared with more invasive procedures such as fistulotomy or advancement flaps.
Effective and safe
MSCs were first used in Spain in 2003 to successfully treat a young women with a complex fistula with five perianal tracts converging into a rectovaginal fistula. The investigators injected a single dose of 9 x 106 MSCs into the site, and the fistula healed within 3 months.
Since then in multiple clinical trials involving more than 400 patients, injection of MSCs has resulted in fistula closure and complete healing by 8-12 weeks in 50%-85% of patients, Dr. Lightner said.
The treatment effect is also durable, she said, pointing to data from the ADMIRE-CD study, in which 51.5% of Crohn’s disease patients with treatment-refractory complex perianal fistula were healed at 24 weeks following injection of adipose-derived stem cells, compared with 35.6% of controls. At 1 year of follow-up, respective rates of healing were 56.3% vs. 38.6%.
Dr. Lightner also cited a case report of a patient whose fistula remained healed 4 years after receiving MSCs for refractory perianal Crohn’s fistulas.
Although MSCs are derived from healthy donors, they do not bear cellular surface antigens that would instigate a destructive host immune response, and to date, there have been no reports from clinical trials of systemic infections or complications. The most frequently reported adverse events have been injection-site pain in about 12%-15% of patients, and perianal abscess in 5%-13%, with similar frequencies in treatment and control groups.
Dr. Lightner and colleagues are currently exploring additional indications for stem cell therapy with MSCs, including other complex fistula phenotypes, intestinal Crohn’s disease, and ulcerative colitis.