The FISPAC Collaborative Group

A study published today in STEM CELLS Translational Medicine indicates that treating cryptoglandular perianal fistula with autologous adipose-derived stem cells (ASCs) is safe and can in fact promote long-term and sustained healing. This condition affects about two out of every 10,000 people per year — most often, young men — according to the National Institutes of Health. While most patients can be treated successfully with surgery, there is a a high rate of recurrence and frequent side effects such as fecal incontinence and, thus, impaired quality of life.

This new study, led by Damian García-Olmo, M.D., and Mariano García-Arranz, Ph.D., of the Instituto de investigación Sanitaria-Fundación Jiménez Díaz, Madrid, was a follow-up to previous studies conducted by the same team. “Seventeen years ago, we began to explore the use of ASCs as a treatment option for patients with complex perianal fistula, hypothesizing that the ASCs’ immunomodulatory and anti-inflammatory capabilities could contribute to the healing process,” Dr. García-Arranz said. “In phase I and II studies, the use of autologous ASCs was proven to be safe for the treatment of fistulas having both a cryptoglandular and Crohn origin. However, a phase III clinical trial we conducted to study cryptoglandular fistula using autologous ASCs failed to find an advantage of the intervention over the control group, possibly owing to issues related to the use of the cell product and trial design.”

This latest study aimed to determine the efficacy of autologous ASCs for the treatment of cryptoglandular complex perianal fistula and to correct the design errors of the previous phase III trial (most of which were related to the manipulation of the cell product and poor selection of patients).

The multicenter, randomized, single-blinded clinical trial was conducted in six institutions from the Spanish Cell Therapy Network (TerCel), a national collaborative translational research organization. Included were 57 patients, 44 of whom were categorized as belonging to the “intent to treat” group. Of these, 23 patients received 100 million ASCs plus intralesional fibrin glue; a second group (21 people) received fibrin glue only, both after a deeper curettage of the fistula tracks and closure of internal openings.

Unlike previous studies, in this study the ASCs were expanded using human platelet lysate in the culture media, which may have the advantage of avoiding the use of animal-derived factors, the researchers said.

After one year of follow-up, no differences were found between patients receiving cells and those of the control group. But at the two-year follow-up, a significant change was observed: Seven of the cured patients from the control group showed recurrence, as compared to only one patient from the cell group.

“Hence, the final results indicate that upon long-term evaluation, twice as many patients treated using autologous ASCs plus fibrin glue had a fully cured fistula, in comparison with fibrin glue alone (50 percent ASC group versus 26 percent control group),” Dr. García-Arranz said.

“However,” cautioned Dr. García-Olmo, “the treatment only seems to provide an advantage over a good surgical protocol at two years after treatment, and then the results are similar to what we saw in previous clinical trials using autologous mesenchymal stem cells.”

“These results show that use of autologous mesenchymal stem cells treatment for complex perianal fistula can be a safe adjunct to surgery, providing valuable information that deserves further study,” said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

The full article, “Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: A randomized clinical trial with a long-term follow-up,” can be accessed at https://stemcellsjournals.onlinelibrary.wiley.com/doi/10.1002/sctm.19-0271.

About STEM CELLS Translational Medicine: STEM CELLS Translational Medicine (SCTM), co-published by AlphaMed Press and Wiley, is a monthly peer-reviewed publication dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices. SCTM is the official journal partner of Regenerative Medicine Foundation.

About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes two other internationally renowned peer-reviewed journals: STEM CELLS® (http://www.StemCells.com), celebrating its 37th year, is the world’s first journal devoted to this fast paced field of research. The Oncologist® (http://www.TheOncologist.com), also a monthly peer-reviewed publication, entering its 24th year, is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. All three journals are premier periodicals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines.

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About Regenerative Medicine Foundation (RMF): The non-profit Regenerative Medicine Foundation fosters strategic collaborations to accelerate the development of regenerative medicine to improve health and deliver cures. RMF pursues its mission by producing its flagship World Stem Cell Summit, honouring leaders through the Stem Cell and Regenerative Medicine Action Awards, and promoting educational initiatives.