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

Table 1 Composite of autologous adipose tissue derived stem cell therapy trials

Author	Yerr of study	Fistula site	Type of study	Study population	Method of administration	Healing type of fistula	Safety	Outcome
García-Olmo et al[5]	2003	RV	Case Report	1	Injection of cells into rectal mucosa	Fully healed	No AE or SAE	Complete resolution at 1 wk with closure still at 3 mo
Lee et al[6]	2013	TS SS IS ES	Clinical Trial, Phase II Multi-center	33	Fistula tract was curetted and irrigated and then ASCs were injected into the submucosa of tract and opening	27 of 33 patients with complete fistula healing at 8 wk 1 of 7 without complete healing had healing after 2nd dose 5 of 33 patients with > 50% closure	60% postoperative pain 19% anal pain -7% anal bleeding 1 patient with exacerbation of disease 1 patient with peritonitis from enteritis from CD	79% patients with complete closure after first dose
Cho et al[7]	2013	TS SS ES	Clinical Trial, Phase I Multi-center	10	Tract curettage was performed and internal opening was closed. Then, subcutaneous adipose tissue collected by liposuction was injected into the fistula tract wall and the surrounding internal opening	Group 1: Three patients with partial closure Group 2: Two patients with complete healing Group 3: One patient with complete healing, one with partial healing	13 AE in 7 patients which were not related to study drug: pain, diarrhea 2 patients SAE: enterocolitis, infliximab administration for new fistulas unrelated to target fistula	All patients with complete closure at 8 wk had sustained complete healing at 8 mo 50% patients after single injection with complete healing
Cho et al[8]	2015	TS SS ES	Clinical Trial, Phase II Multi-center	43	Tract curettage was performed and internal opening was closed. Then, subcutaneous adipose tissue collected by liposuction was injected into the fistula tract wall and the surrounding internal opening. This was done on a primary endpoint of 8 wk; then a retrospective clinical study was conducted looking at patient outcomes after 2 yr	41 of 43 patients were enrolled in the retrospective clinical study After excluded patient: 27 of 33 patients with complete closure	53 AE in 30 patients: abdominal pain (17.1%), eczema (9.8%) exacerbation of disease (9.8%), anal inflammation (7.3%), diarrhea (7.3%), fever (7.3%)	At 12 and 24 mo, respectively, 80% (P ≤ 0.0001) and 75% (P ≤ 0.001) of patients continued to have complete closure
Dietz et al[9]	2017	TS SS IS	Clinical Trial, Phase I Multi-center	12	Delivered ASC to the fistula through attachment of bioabsorbable matrix for surgical placement (MSC-MATRIX) through intraoperative placement	9 of 12 patients with complete healing at 3 mo 10 of 12 patients with compete healing at 6 mo	1 SAE from CD not study (debridement of granulation tissue of fistula tract) 2 AE: seromas at site of fat collection 11 AE: due to underlying CD	83.3% patients at 6 mo with complete healing after MSC-MATRIX placed

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.