Systematic Review of Animal Models Used in Research of Origins and Treatments of Fecal Incontinence

Evers, Judith; Jones, James F.; O’Connell, P. Ronan

doi:10.1097/dcr.0000000000000841

Cited by 5 publications

(6 citation statements)

References 69 publications

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“…After dissection, the sphincter wound was repaired with interrupted sutures using 5-nylene ( Figure 1 ). The IAS specimen was harvested near the anal verge via removal from the distal rectum 1 week after cryoinjury, while considering the different myogenic features of SMCs in the IAS from those in the rectum [ 2 , 25 ]. After harvesting, all experimental animals were euthanized using carbon dioxide gas.…”

Section: Methodsmentioning

confidence: 99%

“…Regenerative medicine using cells has evolved as an optional treatment for anal incontinence (AI) [ 1 ]. According to previous systematic reviews of AI cell therapy, most experimental studies have been performed using animal models associated with injury or damage to the external anal sphincter (EAS) or a nerve [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Only Frudinger et al [ 4 , 5 ] have shown increased resting pressure, without establishing an association with injected autologous skeletal muscle-derived cell injection into SMCs at the cellular level. The current status of the regenerative approach using SMCs for the IAS is associated with a low specificity based on the studies involved [ 2 , 3 ]. The histologic and myogenic functions of SMCs in an IAS differ from those of skeletal muscle cells in an EAS [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Differentiation of Adipose-Derived Stem Cells into Smooth Muscle Cells in an Internal Anal Sphincter-Targeting Anal Incontinence Rat Model

Kim

Lee

et al. 2023

JCM

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Objective: Studies on development of an anal incontinence (AI) model targeting smooth muscle cells (SMCs) of the internal anal sphincter (IAS) have not been reported. The differentiation of implanted human adipose-derived stem cells (hADScs) into SMCs in an IAS-targeting AI model has also not been demonstrated. We aimed to develop an IAS-targeting AI animal model and to determine the differentiation of hADScs into SMCs in an established model. Materials and Methods: The IAS-targeting AI model was developed by inducing cryoinjury at the inner side of the muscular layer via posterior intersphincteric dissection in Sprague–Dawley rats. Dil-stained hADScs were implanted at the IAS injury site. Multiple markers for SMCs were used to confirm molecular changes before and after cell implantation. Analyses were performed using H&E, immunofluorescence, Masson’s trichrome staining, and quantitative RT–PCR. Results: Impaired smooth muscle layers accompanying other intact layers were identified in the cryoinjury group. Specific SMC markers, including SM22α, calponin, caldesmon, SMMHC, smoothelin, and SDF-1 were significantly decreased in the cryoinjured group compared with levels in the control group. However, CoL1A1 was increased significantly in the cryoinjured group. In the hADSc-treated group, higher levels of SMMHC, smoothelin, SM22α, and α-SMA were observed at two weeks after implantation than at one week after implantation. Cell tracking revealed that Dil-stained cells were located at the site of augmented SMCs. Conclusions: This study first demonstrated that implanted hADSc restored impaired SMCs at the injury site, showing stem cell fate corresponding to the established IAS-specific AI model.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differentiation of Adipose-Derived Stem Cells into Smooth Muscle Cells in an Internal Anal Sphincter-Targeting Anal Incontinence Rat Model

Kim

Lee

et al. 2023

JCM

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“…Furthermore, FI cell treatments [ 16 - 19 ] using bone mesenchymal stem cells (MSCs), adipose stem cells (ASCs), myoblasts, and a combined treatment strategy [ 20 - 24 ] have been reported functional improvement in the injured sphincter. However, these studies for cell therapy showed a bias and lacked data for clinical use as reported by the previous systematic reviews [ 25 - 27 ]. Data on the regeneration of IAS associated with basal tone was also limited, and most cell therapy studies were performed on animal models for the skeletal muscle of EAS or nerve damage [ 25 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, these studies for cell therapy showed a bias and lacked data for clinical use as reported by the previous systematic reviews [ 25 - 27 ]. Data on the regeneration of IAS associated with basal tone was also limited, and most cell therapy studies were performed on animal models for the skeletal muscle of EAS or nerve damage [ 25 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

A systematic review of translation and experimental studies on internal anal sphincter for fecal incontinence

Kim

Lee

et al. 2022

Ann Coloproctol

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The complexity in the molecular mechanism of the internal anal sphincter (IAS) limits preclinical or clinical outcomes of fecal incontinence (FI) treatment. So far, there are no systematic reviews of IAS translation and experimental studies that have been reported. This systematic review aims to provide a comprehensive understanding of IAS critical role in FI. Previous studies revealed the key pathway for basal tone and relaxation of IAS in different properties as follows; calcium, Rho-associated, coiled-coil containing serine/threonine kinase, aging-associated IAS dysfunction, oxidative stress, renin-angiotensin-aldosterone, cyclooxygenase, and inhibitory neurotransmitters. Previous studies have reported improved functional outcomes of cellular treatment for regeneration of dysfunctional IAS, using various stem cells, but did not demonstrate the interrelationship between those results and basal tone or relaxation-related molecular pathway of IAS. Furthermore, these results have lower specificity for IAS-incontinence due to the included external anal sphincter or nerve injury regardless of the cell type. An acellular approach using bioengineered IAS showed a physiologic response of basal tone and relaxation response similar to human IAS. However, in both cellular and acellular approaches, the lack of human IAS data still hampers clinical application. Therefore, the IAS regeneration presents more challenges and warrants more advances.

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Jelaković¹,

Čuković‐Čavka²

2018

Clinical Gastroenterology

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Systematic Review of Animal Models Used in Research of Origins and Treatments of Fecal Incontinence

Abstract: Validated animal models representing the main etiologies of fecal incontinence exist, but no animal model to date represents the whole pathophysiology of fecal incontinence. Therefore, the individual research questions still dictate the choice of model and species.

Cited by 5 publications

References 69 publications

Differentiation of Adipose-Derived Stem Cells into Smooth Muscle Cells in an Internal Anal Sphincter-Targeting Anal Incontinence Rat Model

Differentiation of Adipose-Derived Stem Cells into Smooth Muscle Cells in an Internal Anal Sphincter-Targeting Anal Incontinence Rat Model

A systematic review of translation and experimental studies on internal anal sphincter for fecal incontinence

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