One more chance of fistula healing in inflammatory bowel disease: Stem cell therapy

Table 3 Composite of allogeneic adipose tissue derived stem cell therapy trials

Author	Year of study	Fistula site	Study population	Method of administration	Healing type of fistula (unhealed, partially, fully)	Safety	Outcome
García-Arranz et al[11]	2016	RV	10	Tract curettage was performed and vaginal or rectal flap added with intralesional injection of 20 million allogeneic adipose stem cells injected into the fistula tract and vaginal submucosa. If complete healing was not seen at 12 wk, patients were re-administered stem cells	2 patients with complete healing at 12 wk 2 patients with complete healing from the 8 patients with second administration of stem cells 9 patients at some point during the study had fistula healing	No SAE or AE	3 of 5 patients included in total (others excluded during study) remained healed at 52 wk, showing 60% efficacy
de la Portilla et al[12]	2013	Perianal	24	Intralesional fistula tract injection with stem cells with repeat administration at 12 wk with dose escalation if incomplete closure	38.1% patients achieved complete closure at week 12 65.3% patients achieved complete closure at week 24	13 patients with 32 AE and of these 5 were treatment related: anal abscess (3 patients), pyrexia (1 patient), uterine leiomyoma (1 patient)	69.2% patients had fistula reduction at 24 wk
Panés et al[13]	2016	TS SS IS ES	212	Patient randomized into two groups: Placebo with 24 ml saline Intralesional injection of Cx601 cells Study conducted over 24 wk	50% patients with Cx601 vs 34% placebo achieved complete fistula healing and remained closed at week 24 (P = 0.024)	TEAE: proctalgia, anal abscess, and nasopharyngitis 5% in treatment group and 6% in placebo group withdrew	Cx601 is effective and safe for treatment of refractory fistulizing CD
Panés et al[14]	2017	TS SS IS ES	212	This was a continuation of the above study from 24 to 52 wks Patient randomized into two groups: Placebo with 24 ml saline Intralesional injection of Cx601 cells	35%-40% patients withdrew before end of study 59.2% patients with Cx601 vs 41.6% patients with placebo (P = 0.013) achieved clinical remission 56.3% patients with Cx601 versus 38.6% patients with placebo (P = 0.010) achieved combined remission	TEAE: 76.7% in treatment group and 72.5% in control group: anal abscess/fistula 8.7% treatment group and 8.8% control group withdrew	Cx601 is safe and effective for treatment refractory complex perianal fistulas in patients with CD
Wainstein et al[15]	2018	TS IS Pouch-vaginal	9 (2 of 9 patients had 2 fistulas, so total fistula count was 11)	Two part study including: Examination under anesthesia, fistula mapping, drainage and seton placement Setons were removed 4-6 wks afterwards with ASC injected with biological plug formation	Complete healing in 10 of 11 fistulas Partial healing in 1 of 11 fistulas	No AE or SAE	Fistulizing disease can be treated successfully with a multi-approach treatment including ASCs, platelet rich plasma, and endorectal advancement flaps

CD: Crohn’s disease; ASC: Autologous stem cells; TS: Transsphincteric; SS: Suprasphincteric; IS: Intersphincteric; ES: Extrasphincteric; RV: Rectovaginal; AE: Adverse events; SAE: Serious adverse events; TEAE: Treatment emergent adverse event.