Stem cell therapy for faecal incontinence: Current state and future perspectives

Table 4 Overview and concise review of different published studies related to faecal incontinence and stem cell therapy in animal models

Ref.	Animal	N	Randomized	Type of SC	Compared to	FI model	Repair?	Treatment	Effect measure	Follow up	Principal Results	Security concerns
[35]	Rats	32	No	AUT/ALLOG BM-MSCs	Sham injury Injury + SSF	Surg section	Surg	Inj IE	Histology In vitro contractility	30 d	↑ muscular area ↑ Electric response and relaxing	No
[36]	Rats	15	No	MDSC AUT	No injury Crioinj/crioinj + SCs	Crioinjury	No	Inj IE	Histology In vitro contractility	7 d	SC survive + myofibre differentiation ↑ contractility (NSS)	No
[37]	Rats	??	No	Myoblast ALLOG	Subcutaneous levator ani thig muscle	No	No	Inj levator ani	Histology	??	SC survivor injury necessary for myofibre formation	No
[38]	Rab-bits	31	No	hUSCs SYNG BM-MSCs ALLOG	Culture medium Saline	Section	No	Inj IE 2 wk later	Clinic EMG Histology	2 wk	BM-MSC: better continence ↑ act SS ↑ muscle	No
[39]	Rats	120	Yes	MDSC ALLOG	Saline	Surg section EAS	Surg	Inj IE	Contractility	13 wk	↑ SS contractility 7/90 d only repaired	No
[40]	Rats	4	No	Myoblasts ALLOG	None	No	No	Inj IE	Histology	10 d	SC survival and integration in sane host tissue	No
[41]	Rabbits	21	No	MDSC AUT	Saline	Surg section EAS	No	Inj IE 3 wk later	Clinic Histology EMG + MAR	2 mo 6 mo (control)	↑ continence since 4w Miotube + myofibre (4wk), SC Survival, ↓ Cd3 and cd34 cells, ↑ proliferate ↑ SS MAR and EMG since 4wk and grew	No
[42]	Rats	224	No	BM-MSCs ALLOG local/systemic	PBS local/Syst	Surg section EAS	Surg	Inj IE/systemic	Mollecular Histology Neurophisiology	21 d	Local: ↑ECM acute phase ↑ fibers SS detected 24-48 h (no later) ↑ activity	↑ mortality nearly SS systemic
[43]	Rats	70	Yes	BM-MSCs ALLOG local/systemic	PBS local/Syst/Sham injuries	Surg section PNC	No	Inj IE/systemic	MAR + EMG	10 d	IM/IV improve MAR, IV MAR non after PNC No SC survivor	No
[46]	Dogs	10	No	Myoblast AUT + bioengineering	SC/nothing	Excision 25% AS	No	Inj IE 3 mo later	CMAP/MAR Histology	3 mo	↑ MAR (non SS) Foreign body reaction	No
[47]	Rats	33	No	MDSCs ALLOG	Sham control (9 vs 24 rats)	Surg section	Surg	Inj IE	Migration lung-liver AS histology	30 d	No migration	2 benign local foci
[48]	Rats	45	No	Myoblast SYNG	Uninjured crioinj + PBS	Crioinjury	No	Inj IE	Histology/MAR	2 mo (histo) 6 mo (function)	Restitutio (60 d), SC integrated ↑ MAR 30 d, SS from 60 d	No
[49]	Rats	33	Yes	MDSC ALLOG	PBS	Surg section (Proctoepisio)	Surg	Inj IE	MAR + EMG Histology	4 wk	Improve SS EMG + MAR 2wk not 4wk No differences in sphincter thickness	No
[50]	Rabbits	12	Yes	MDSC AUT	Saline	Surg section EAS	No	Inj IE 3wk later	MRI/MAR + EMG Histology	4 wk	Labelled cells in MRI + areas, iron + myofibre ↑ ES MAR y EMG	No
[51]	Rats	??	No	Neural enteric progenitors XENOG	No injury/Crio/Crio + SCs	NO	No	BE: NPC + IAS cells + bilayer	Histology/EMG	4 wk	↑ neovascularization normal functioning	No
[53]	Rats	50	Yes	BM-MSCs ALLOG local/systemic	Saline Uninjured	Excision 25% AS	No	Inj IE/serial IV 24 h/3 wk later	MAR Histology (immunofluoresc)	5 wk	-↑ P 10d MSCs, 5wk MSC > Saline but no differences with uninjured Histology: ↓gap, fibrosis, scar/ Delayed 3wk no efficacy	No
[54]	Rats	40	Yes	MDSC ALLOG	PBS	Surg section	Surg	Inj IE	Histology	3 mo	No differences between groups	No
[55]	Dogs	15	No	Myobl AUT + PCL beads	PBS Uninjured	Excision 25% AS	No	Inj IE 1mo later	MAR Histology	3 mo	↑ SS MAR (50% basal) SC survival + differentiation	No
[56]	Dogs	10	Yes	Myoblast AUT (A)	(B) Myob aut + PCL beads with bFGF	Excision 25% AS	No	Inj IE 1 mo later	MAR/CMAP Histology	3 mo	↑ SS MAR + CMAP B > A SC en 40% (A) vs 100% (B)	No
[57]	Rats	80+ 20	Yes	MDSC ALLOG + hidrogel	Nothing PBS-hydrogel Collagen/No injury	Surg Section	No	Inj IE	Contractility Histology	3 mo	↑Contract and ↑ all F-U in SC-Hydrogel ↑ SS Muscle SC-Hydrogel; ↓ inflammation SC-Hydrogel and collagen	No
[58]	Rab-bits	16	No	MDSC AUT	Only EAS scafold	Total EAS excision	No	EAS sustitution	Histol (every 3 mo) EMG 2 yr	2 yr	No inflammation-reject, improve SS 3-6mo Improve EMG (no statistics provided)	No
[59]	Rats	58	Yes	BM-MSC ALLOG + electrostim	No treatment Elecrostimulation	Excision 50%	No	Inj IE + electrostim	Histology/MAR	4 wk	4wk, electrostimulation + 1 dose MSCs: ↑ muscle in injury area ↑ resting P compared with other groups	No
[60]	Rats	32	No	BM-MSCs ALLOG BM mononuclear	Sham surgery SSF	Surg section	Surg	Inj IE	Histol/morphometry/MAR In vitro contractility	30 d	SC ↑ regen and SS contractility No differences between SC SC survive 30 d	No
[61]	Rats	32	Yes	BM-MSCs ALLO + SDF-1 (simult/deferred)	No treatment SDF-1	Excision 50%	No	Inj IE + SDF-1 ± gelatin scaffold	Histology/MAR	4 wk	SDF-1 +/- SCs: ↑ resting P and %muscle and muscle organization and ↓ fibrosis (SS)	No
[76]	Rabbits	20	No	Neural enteric Progenitors AUT	No treatment Sham injury	Excision 50% IAS	No	Sustitution (biosphincter) 6-8 wk later	Histology/MAR	3 mo	Functional improvement since 1mo, SS with others Regeneration, neovascularization and innervation	No
[63]	Rats	56	Yes	BM-MSCs ALLOG + SDF-1 (deferred)	No treatment SDF-1	Excision 50%	No	Inj IE + SDF-1 ± gelatin scaffold	Histology Morphometry MAR Cytoquines	8 wk	Plasmid +/- SCS: ↑ MAR, muscle organization Plasmid: ↑ muscle mass SDF-1 sufficient for repairing without SC+ / -scaffold	No
[64]	Rats	36	Yes	ASCs SYNG	Conventional suture	Surg section	Yes/No	Inj IE biosuture	Histology/MAR	7 d	No functional differences SC survivor and migration to injury	No
[65]	Rats	58	Yes	Human ASCs	SSF Bulkamid (hydrogel)	Surg section	Surg	Inj IE	MAR micro-CT Histology	4 wk	Functional: ↑ SS ASCs and grew: no differences between carriers Morphology: no differences in muscle, > inflammation if ASCs, micro-CT correlation	No
[67]	Rats	60	No	BM-MSCs ALLOG ± electroacupunct	Sham injury Elecroacupunture SSF acupuncture	Surg section	No	Inj IV	Morphology	14 d	SC+EA ↑vessels, fibroplasia and ↓ inflammation ↑ muscle SS and homing growth factors (SS). Electroacupunct promotes homing	No

AUT: Autologous; ALLOG: Allogeneic; SYNG: Syngeneic; XENOG: Xenogeneic; SSF: Saline solution; Surg: Surgical; Inj: Injection; IE: Intrasphincteric; Crioinj: Cryoinjury; NSS: Non-statistically significant; SS: Statistically significant; ??: Unknown; ECM: Extracellular matrix; AS: Anal sphincter; Proctoepisio: Proctoepisiotomy; NPC: Neural progenitor cells; Immunofluoresc: Immunofluorescence; P: Pressure; PCL: Polycaprolactone; F-U: Followup; Histol: Histology; Simult: Simultaneous; Electrostim: Electrostimulation; Electroacupunt: Electroacupuncture.