Allogeneic expanded adipose‐derived stem cells in the treatment of rectovaginal fistulas in Crohn’s disease

Abstract

Aim Crohn's disease (CD)‐related rectovaginal fistulas (RVFs) are rare, challenging to treat and associated with a high morbidity. Due to a significant lack of data, we aimed to analyse the safety and feasibility of allogeneic adipose‐derived stem cells (ASCs) in the treatment of CD‐related RVF. Method Four consecutive patients with CD‐related RVF underwent treatment with expanded allogeneic ASCs extracted from a healthy donor in a tertiary referral centre in 2019. None of the patients had an intestinal diversion at the time of the treatment. Follow‐up was performed 6 months postoperatively. Results The median operation time was 45 min with a median hospital stay of 3 days. No intra‐operative complications occurred. Three patients (75%) developed recurrent RVF after a median follow‐up of 19 days. Two patients required surgical treatment including loose seton drainage due to discharge and pain. One patient developed recurrence of symptoms after 10 days, but refused further surgical therapy. Only one patient (25%) showed healing of the RVF, with re‐epithelialization of both the vaginal and rectal opening and absence of clinical symptoms. Conclusion Expanded allogeneic ASC therapy represents a novel safe treatment option for CD‐associated RVF. Although efficacy appears limited, further controlled studies are required to draw robust conclusions.

Efficacy and Safety of Mesenchymal Stem/Stromal Cell Therapy for Inflammatory Bowel Diseases: An Up-to-Date Systematic Review

“…No AEs related to MSC therapy were observed. Similar to other studies examining MSC therapy in RVF [ 33 , 35 ], this study was limited by small sample size, lack of blinding, and lack of control group. Additionally, patients in this study were required to discontinue biologic therapy prior to the study in order to prevent the benefits of biologic therapy from being interpreted as efficacy for MSC therapy.…”

“…Nikolic et al [ 35 ] performed a small pilot study utilizing Alofisel ® , (darvadstrocel, Takeda), a product comprised of allo-ASCs already approved for use in the European Union for PFCD, on four patients with RVF due to CD. Only one patient (25%) experienced sustained clinical healing of RVF on rectovaginal exam 6 months after treatment.…”

“…One condition in which local MSC therapy has not been established to be consistently effective is RVF [ 33 , 35 , 37 ]. It has been hypothesized that RVF is particularly difficult to treat due to the shortness of the tracts and thinness of the rectovaginal membrane, thus overall decreasing the volume and amount of MSCs that can be delivered relative to non-rectovaginal fistulae [ 33 , 35 ]. More studies focusing specifically on RVFs and their idiosyncrasies are necessary moving forward.…”

A Systematic Review of the Patient Burden of Crohn’s Disease-related Rectovaginal and Anovaginal Fistulas

“…Fistulizing CD is characterized by variable clinical presentations [3], but patients with RVF almost always have severe discomfort and pain, and may suffer psychological effects, including anxiety or poor body image due to malodorous drainage uid [4,7,6]. For many, the natural history includes frequent recurrence after treatment and long episodes of actively draining stulas [3].…”

Allogeneic expanded adipose‐derived stem cells in the treatment of rectovaginal fistulas in Crohn’s disease, by Nikolic et al

“…In January's edition of Colorectal Disease , Nikolic et al present their study on the use of allogeneic adipose‐derived mesenchymal stem cells (ASC) to treat rectovaginal fistula (RVF) in Crohn’s disease [1]. I chose this paper as there is enormous interest in the use of ASCs in across surgical disciplines including colorectal surgery, for example in fistula in ano and more recently for faecal incontinence.…”