No 10 CROHNS ......... The State of Play of Stem Cells in Inflammatory Bowel Disease A conversation with researcher and surgeon Amy Lightner, MD FACEBOOKTWITTERLINKEDINPINTERESTEmail
The introduction of infliximab in 1998 and the subsequent addition of more biologic products marked a new era in the treatment of inflammatory bowel disease (IBD), significantly improving medical management.
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However, all biologics have side effects that limit their use, and they are effective in no more than half of IBD patients. Patients who become refractory to medical management eventually need surgery; one-third of patients with ulcerative colitis and about two-thirds of patients with Crohn’s disease still require a major abdominal operation, with the inherent prospect of complications and reduced quality of life.
There is a clear need for improved IBD treatments. Stem cell therapy, with its potential for suppression of overactive immune response and for healing inflamed tissue, is emerging as a promising IBD treatment alternative.
Amy Lightner, MD, is a leading translational researcher and clinical trials director in stem cell therapy for Crohn’s disease, as well as an expert in regenerative surgery and its application to IBD. In 2019, she was recruited from the Mayo Clinic to become an Associate Professor of Surgery and Associate Chief of Surgical Research in Cleveland Clinic Digestive Disease & Surgery Insitute’s Department of Colon and Rectal Surgery. Dr. Lightner also is the Primary Investigator of the surgical inflammatory bowel disease translational laboratory.
Dr. Lightner spoke with Consult QD about her work and the state of play of stem cells in IBD.
Why do stem cells particularly show promise for IBD?
We’ve done a lot of phase I, II and III clinical trials in perianal fistulizing Crohn’s disease, and stem cells have shown superior efficacy to conventional therapy with medications and surgical intervention. There have been no safety issues to date. We don’t know exactly why stem cells work, but they seem to migrate to sites of inflammation or injury. They then seem to release cytokines that recruit other cells to treat inflammation and immunity. This kind of action seems to increase T regulatory cells and interleukin 10, which is important in Crohn’s disease. It probably alters the macrophage ratio, which also helps healing in Crohn’s disease. So there seems to be something on a cellular level that’s happening that certainly makes stem cells effective, particularly for Crohn’s.
Do mesenchymal or hematopoietic stem cells have a particular advantage or efficacy?
All the stem cell trials to date in IBD have used mesenchymal stem cells. Access to mesenchymal stem cells is easier. You can harvest adipose tissue or bone marrow tissue. It can be autologous or allogeneic.
Does the tissue donation site make a difference in efficacy?
They’ve never been directly compared. There have been clinical trials using both, but the clinical trial design was different, so we can’t really compare across trials. There’s probably easier access to adipose tissues, so it’s more often used. Fistulas are in ischiorectal fat, so the thought would be that if you inject stem cells derived from fat tissue, you could potentially signal to the local micro environment in a superior way than when using bone marrow-derived stem cells.
Does localized injection of stem cells have an advantage over systemic administration?
All of the perianal Crohn’s disease trials have used local delivery of stem cells, and that’s clearly safe and effective. The challenge with delivering stem cells intravenously is they have pulmonary trappings, so they get trapped in the lung when we inject them into the venous system. Arterial delivery is likely effective, but you need interventional radiology for targeted delivery. There have only been two small pilot studies done on that. So we’re going to be rolling out a phase I trial doing arterial delivery for intestinal Crohn’s disease.
Do stem cells have the same potential in ulcerative colitis as in fistulizing Crohn’s disease?
I imagine that they would, given that ulcerative colitis involves an aberrant immune response or level of inflammation. So stem cells theoretically should also be effective for ulcerative colitis, but it hasn’t been studied yet.
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