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.