Recurrent anal fistulae: Limited surgery supported by stem cells

Table 1 Study data

ID	Sex	Age (yr)	Crohn’s disease	Park’s classification	Previous surgical attempts	Initial incontinence score (Wexner)	Surgical technique	Fibrin glue	Cells	Response 8th week	Incontinence score 8th week	Healing one year after
1	Male	58	No	III	8	1	Flap + deep curettage	No	eASC	Yes	0	Yes
2	Male	43	No	II	4	Unknown	IO closure + partial fistulectomy	Yes	eASC	Yes	4	No
3	Male	76	No	III	5	0	IO closure + deep curettage	Yes	eASC	Partial	0	No
4	Male	57	No	III	12	0	IO closure + deep curettage	Yes	eASC	Yes	0	Yes
5	Female	45	Yes	IV (multiple tracts)	6	12	IO closure + deep curettage	Yes	eASC	Partial	8	Yes
6	Male	35	Yes	II (stenosis)	5	Unknown	IO closure + deep curettage	No	eASC	No	0	No
7	Male	40	Yes	III	3	Unknown	IO closure + deep curettage	Yes	eASC	Yes	0	Yes
8	Male	59	No	II	11	13	Flap + deep curettage	No	eASC Allog	Partial	5	No
9	Male	50	No	I	3	Unknown	Fistulotomy	Yes	eASC	Yes	0	Yes
10	Female	28	No	III	5 + ileostomy	Not evaluable	Flap + partial fistulectomy	Yes	SVF	Yes	Not evaluable	Yes

IO: Internal opening; eASC: Expanded adult stem cells; Allog: Allogeneic; SVF: Stromal vascular fraction.

Table 2 Published studies on stem cell therapy for anal fistulae

Ref.	Year	Condition	Study design	Cell source	Cell quantity (dose)	Intervention model
García-Olmo et al[11]	2003	Recto-vaginal fistula in Crohn’s disease	Case report	Autologous eASC	1 × 107	Single arm
García-Olmo et al[12]	2005	Enterocutaneous, recto-vaginal, perianal fistula in Crohn’s disease	Phase I	Autologous eASC	1-3 × 107 re-suspended in fibrin glue	Single arm
García-Olmo et al[13]	2009	Perianal fistula with or without Crohn’s disease	Phase II	Autologous eASC	Not specified	Two arms: fibrin glue, fibrin glue + eASC
García-Olmo et al[22]	2010	Recto-vaginal fistula in Crohn’s disease	Case report	Allogenic eASC	Not specified	Single arm
Ciccocioppo et al[25]	2011	Enterocutaneous and complex perianal fistula in Crohn's disease	Case report	Expanded autologous bone marrow	5 × 107	Single arm
Cho et al[24]	2012	Perianal fistula in Crohn’s disease	Phase I	Autologous eASC	Not specified	Single arm: dose escalation study
Herreros et al[14]	2012	Complex perianal fistula without Crohn’s disease	Phase III	Autologous eASC	2 × 107 then 4 × 107 if no effect	Three arms: fibrin glue, eASC, fibrin glue + eASC
Herreros et al[14]	2012	Complex perianal fistula without Crohn’s disease	Observational	Autologous eASC	2 × 107 then 4 × 107 if no effect	Three arms: fibrin glue, eASC, fibrin glue + eASC
Guadalajara et al[23]	2012	Perianal fistula with or without Crohn’s disease	Observational	Autologous eASC	Not specified	Two arms: fibrin glue, fibrin glue + eASC
de la Portilla et al[17]	2012	Perianal fistula in Crohn’s disease	Phase I/II	Allogeneic eASC	2 × 107 then 4 × 107 if no effect	Single arm
Lee et al[20]	2013	Perianal fistula in Crohn’s disease	Phase II	Autologous eASC	Depending on the fistula. Re-dosing (1.5 times) if no effect	Single arm

SAE: Serious adverse events (those requiring hospital admission > 24 h); eASC: Expanded adult stem cells.

Table 3 Outcomes of published clinical experience of stem cell treatment for anal fistula

Ref.	Procedure	No. of patients treated	Healed (n)	Follow-up (mo)	Recurrence (n)	SAE (n)
García-Olmo et al[11]	Closure of IO. Injection in site, without fibrin glue	1	1	3	0	0
García-Olmo et al[12]	Cells resuspended in fibrin glue. Injection in site	9	6	12	Not specified	0
García-Olmo et al[13]	Closure of IO. Injection in site	Fibrin glue: 25 Fibrin glue + eASC: 24	Fibrin glue: 3 Fibrin glue + eASC: 17	12	Fibrin glue: 0 Fibrin glue + eASC: 2	4 (1 related to fibrin glue, others unrelated)
García-Olmo et al[22]	Closure of IO. Injection in site, without fibrin glue	1	1	36	1	0
Ciccocioppo et al[25]	Four injections in site	10	7	12	0	0
Cho et al[24]	Closure of IO and fibrin glue. Injection in site	9	3	15	0	0
Herreros et al[14]	Closure of IO. Injection in site	eASC: 64 Fibrin glue + eASC: 60 Fibrin glue: 59	eASC: 27 Fibrin glue + eASC: 24 Fibrin glue: 23	6	eASC: 0 Fibrin glue + eASC: 4 Fibrin glue: 0	4 unrelated to study treatment
Herreros et al[14]	Closure of IO. Injection in site	Not specified	eASC: 57% Fibrin glue+ eASC: 52.4% Fibrin glue: 37.3%	12	Not specified	1 unrelated to study treatment
Guadalajara et al[23]	Closure of IO. Injection in site	Fibrin glue: 13 Fibrin glue + eASC: 21	Fibrin glue: 3 Fibrin glue + eASC: 10	38	Fibrin glue: 1 Fibrin glue + eASC: 5	0
de la Portilla et al[17]	Closure of IO. Injection in site, without fibrin glue	24	9	4	Not specified	2 unrelated to study treatment
Lee et al[20]	Injection in site and fibrin glue	43	27	12	4	0

IO: Internal opening; SAE: Serious adverse events (those requiring hospital admission > 24 h); eASC: Expanded adult stem cells.