There’s one main way to treat inflammatory bowel disease (IBD): Control inflammation by whipping the immune system into shape, a process that can go haywire or fail to work. But what if the body could promote healing by regenerating new tissue?
That’s the promise — and the challenge — of stem cell therapy, an experimental treatment for Crohn’s disease and ulcerative colitis that’s been studied in this context for at least two decades. The treatment isn’t ready for routine clinical use, and some studies have failed to uncover any benefit. But other research suggests that it has potential, especially in Crohn’s disease.
“A therapy that could promote mucosal healing without immune suppression would obviously be really appealing,” said gastroenterologist Sarah Streett, MD, of Stanford University School of Medicine in California, who’s studying stem cell therapy for Crohn’s disease fistulas. “That’s the premise of using stem cells.”
Crohn’s Gets Most of the Research Focus
IBD treatments that target inflammation have significant limitations, Streett told MedPage Today. “In addition to fighting infection, inflammation also has an important role in how we regenerate when something has been injured. Current therapies used now to treat IBD inhibit immune activity and suppress inflammation, but they don’t focus on enhancing regeneration.”
Stem cell therapy, according to Streett, has potential because it could help regenerate the mucosal barrier in the gut. “Stem cells can differentiate into epithelial cells, fibroblasts, and other things,” she said. “In vivo and in vitro, they’ve been shown to make angiogenic factors to help with healing and blood flow and alter the immune function in the localized area where they’re placed.”
Among the two most common forms of IBD, Crohn’s disease has gotten the lion’s share of attention in stem cell research versus ulcerative colitis. That’s because researchers focus on “high-risk, high-reward situations,” Streett said. “In ulcerative colitis, the patient can have a colectomy. That is not ever desired by any of us, but it can lead to the cessation of their disease. In Crohn’s disease, that’s not an option.”
Stem Cells Are Investigated in Perianal Fistulas
Streett is an investigator in the industry-funded phase II study STOMP-II that’s examining the use of stem cell therapy in 60 patients with Crohn’s perianal fistulas that haven’t responded to treatment. “Mesenchymal stem cells are cultivated from each patient’s own adipose tissue and put into a bioprosthetic plug, which is then put into the fistula’s tract and sutured in there to create a matrix,” Streett said. The strategy “seems to be really well tolerated, and I’m hopeful about that,” she said. Results are expected later this year or next year.
Streett noted that a much larger 568-patient trial, which relied on donor stem cells to treat Crohn’s perianal fistulas, was a failure. The results of the international ADMIRE-CD II phase III trial were published in 2024. The trial had a “really high” placebo response rate, Streett said, possibly because both the control and intervention groups underwent an exam, curettage, and placement of a drain under anesthesia. This treatment may have promoted healing, she said.
Stem Cell Transplant: A More Drastic Strategy
Autologous hematopoietic stem cell transplantation, which targets the full immune system, is a more intensive approach. Interest in the approach in IBD grew after cancer patients who underwent stem cell transplant procedures saw improvements in immune diseases.
“It didn’t make a difference what immune disease they had. Crohn’s disease, rheumatoid arthritis, multiple sclerosis — all these diseases were improving,” gastroenterologist Louis Cohen, MD, of Icahn School of Medicine at Mount Sinai in New York City, told MedPage Today. “We wanted to take it a step further and ask a question: ‘Well, why does stem cell transplant work?'” he said. “Is it just getting rid of bad cells? Is it possible that it isn’t just getting rid of bad cells, but it’s also using these stem cells to provide good ones?”
His team found evidence that in order for stem cell transplants to be effective, they would have to eliminate bad cells and introduce healthy stem cells to “reprogram the tissue, teach it how to heal.”
Now, Cohen is working with an international consortium to gather long-term data about 200 Crohn’s patients who’ve undergone stem cell transplants. “We want to bring all that data together as part of a single, multicenter study so we can show people what happens to patients not just in the short term but over 5-10 years posttransplant,” he said. “With that data, it’ll help to change policy.”
How Adverse Effects and Cost Fit In
As with anal fistulas, research findings in stem cell therapy for Crohn’s have been mixed so far. Several small studies have reported positive results. However, a small, randomized European study, whose findings were published in 2024, was stopped because the intervention group had more adverse events, including death. Still, the study showed a reduction in disease activity. In response to a subsequent call for hematopoietic stem cell therapy in Crohn’s disease to be halted, Cohen and colleagues defended the therapy: “Stem cell transplantation must be considered for patients with refractory forms of Crohn’s disease when the alternative of no treatment is more devastating.”
In an interview, Cohen said the study raised questions about whether patients with Crohn’s who undergo stem cell transplant with the chemotherapy drug fludarabine fare differently than patients with cancer. He added that researchers are trying to understand the unique adverse effects suffered by Crohn’s patients who undergo the transplants.
As for cost, he noted that the transplants are highly expensive, but long-term care for patients with refractory Crohn’s is also highly costly.
Looking Forward: On the Horizon
What’s next for large-scale stem cell research in IBD?
Gastroenterologist Miguel Regueiro, MD, of Cleveland Clinic Lerner College of Medicine/Case Western Reserve University, told
MedPage Today that “the injection of stem cells into fistula tracts has been part of clinical care in certain countries outside of the U.S.A.”
However, the ADMIRE-CD II trial failed, and Regueiro doesn’t foresee any other large clinical trial for stem cell therapy in fistulas anytime soon. Any regulatory approval would therefore be many years away, said Regueiro, who spoke about stem cell therapy and other treatments for Crohn’s fistulas at the recent 2025 Digestive Disease Week (DDW) conference.
As for stem cell transplants, Cohen said some consortium findings were released at the DDW 2025 conference, and the group may have long-term data as early as this year. What about ulcerative colitis? Like Streett, Cohen noted that the disease can be treated with surgery. Severe Crohn’s, in contrast, can lead to death in extreme cases. Still, there is room to develop a stem cell therapy protocol for ulcerative colitis, he noted. “That would be another goal of our program,” he said. “Not over the next year or two, but maybe over the next 5 years.”
Disclosures
Streett disclosed relationships with Avobis and Direct Biologics.
Cohen disclosed a relationship with Orchard Therapeutics.
Regueiro disclosed relationships with AbbVie, Johnson & Johnson, UCB, Takeda, Pfizer, BMS, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, Boehringer Ingelheim, Roche, Merck, Sanofi, Biocon, and Abivax.
