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Functional Outcome of Human Adipose Stem Cell Injections in Rat Anal Sphincter Acute Injury Model.

ABSTRACT: Anal incontinence is a devastating condition that significantly reduces the quality of life. Our aim was to evaluate the effect of human adipose stem cell (hASC) injections in a rat model for anal sphincter injury, which is the main cause of anal incontinence in humans. Furthermore, we tested if the efficacy of hASCs could be improved by combining them with polyacrylamide hydrogel carrier, Bulkamid. Human ASCs derived from a female donor were culture expanded in DMEM/F12 supplemented with human platelet lysate. Female virgin Sprague-Dawley rats were randomized into four groups (n?=?14-15/group): hASCs in saline or Bulkamid (3 × 105 /60 ?l) and saline or Bulkamid without cells. Anorectal manometry (ARM) was performed before anal sphincter injury, at two (n?=?58) and at four weeks after (n?=?33). Additionally, the anal sphincter tissue was examined by micro-computed tomography (?CT) and the histological parameters were compared between the groups. The median resting and peak pressure during spontaneous contraction measured by ARM were significantly higher in hASC treatment groups compared with the control groups without hASCs. There was no statistical difference in functional results between the hASC-carrier groups (saline vs. Bulkamid). No difference was detected in the sphincter muscle continuation between the groups in the histology and ?CT analysis. More inflammation was discovered in the group receiving saline with hASC. The hASC injection therapy with both saline and Bulkamid is a promising nonsurgical treatment for acute anal sphincter injury. Traditional histology combined with the 3D ?CT image data lends greater confidence in assessing muscle healing and continuity. Stem Cells Translational Medicine 2018;7:295-304.

SUBMITTER: Kuismanen K

PROVIDER: S-EPMC5827744 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Functional Outcome of Human Adipose Stem Cell Injections in Rat Anal Sphincter Acute Injury Model.

Kuismanen Kirsi K Juntunen Miia M Narra Girish Nathaniel N Tuominen Heikki H Huhtala Heini H Nieminen Kari K Hyttinen Jari J Miettinen Susanna S

Stem cells translational medicine 20180131 3

Anal incontinence is a devastating condition that significantly reduces the quality of life. Our aim was to evaluate the effect of human adipose stem cell (hASC) injections in a rat model for anal sphincter injury, which is the main cause of anal incontinence in humans. Furthermore, we tested if the efficacy of hASCs could be improved by combining them with polyacrylamide hydrogel carrier, Bulkamid. Human ASCs derived from a female donor were culture expanded in DMEM/F12 supplemented with human ...[more]

PMID: 29383878

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Project description:BackgroundAnal sphincter injury leads to fecal incontinence. Based on the regenerative capability of laser and human adipose-derived stem cells (hADSCs), this study was designed to assess the effects of co-application of these therapies on anal sphincter recovery after injury.DesignMale rabbits were assigned to equal groups (n?=?7) including control, sphincterotomy, sphincterotomy treated with laser (660?nm, 90 s, immediately after sphincterotomy, daily, 14?days), hADSCs (2?×?106 hADSCs injected into injured area of the sphincter immediately after sphincterotomy), and laser?+?hADSCs. Ninety?days after sphincterotomy, manometry and electromyography were performed, sphincter collagen content was evaluated, and Ki67, myosin heavy chain (MHC), skeletal muscle alpha-actin (ACTA1), vascular endothelial growth factor A (VEGFA), and vimentin mRNA gene expression were assessed.ResultsThe laser?+?hADSCs group had a higher resting pressure compared with the sphincterotomy (p?<?0.0001), laser (p?<?0.0001), and hADSCs (p?=?0.04) groups. Maximum squeeze pressure was improved in all treated animals compared with the sphincterotomized animals (p?<?0.0001), without a significant difference between treatments (p?>?0.05). In the laser?+?hADSCs group, motor unit numbers were higher than those in the laser group (p?<?0.0001) but did not differ from the hADSCs group (p?=?0.075). Sphincterotomy increased collagen content, but the muscle content (p?=?0.36) and collagen content (p?=?0.37) were not significantly different between the laser?+?hADSCs and control groups. Laser?+?hADSCs increased ACTA1 (p?=?0.001) and MHC (p?<?0.0001) gene expression compared with laser or hADSCs alone and was associated with increased VEGFA (p?=?0.009) and Ki67 mRNA expression (p?=?0.01) and decreased vimentin mRNA expression (p?<?0.0001) compared with laser.ConclusionThe combination of laser and hADSCs appears more effective than either treatment alone for promoting myogenesis, angiogenesis, and functional recovery after anal sphincterotomy.

Project description:Background & aimsThe anal sphincters and puborectalis are imaged routinely with an endoanal magnetic resonance imaging (MRI) coil, which does not assess co-aptation of the anal canal at rest. By using a MRI torso coil, we identified a patulous anal canal in some patients with anorectal disorders. We aimed to evaluate the relationship between anal sphincter and puborectalis injury, a patulous anal canal, and anal pressures.MethodsWe performed a retrospective analysis of data from 119 patients who underwent MRI and manometry analysis of anal anatomy and pressures, respectively, from February 2011 through March 2013 at the Mayo Clinic. Anal pressures were determined by high-resolution manometry, anal sphincter and puborectalis injury was determined by endoanal MRI, and anal canal integrity was determined by torso MRI. Associations between manometric and anatomic parameters were evaluated with univariate and multivariate analyses.ResultsFecal incontinence (55 patients; 46%) and constipation (36 patients; 30%) were the main indications for testing; 49 patients (41%) had a patulous anal canal, which was associated with injury to more than 1 muscle (all P ≤ .001), and internal sphincter (P < .01), but not puborectalis (P = .09) or external sphincter (P = .06), injury. Internal (P < .01) and external sphincter injury (P = .02) and a patulous canal (P < .001), but not puborectalis injury, predicted anal resting pressure. A patulous anal canal was the only significant predictor (P < .01) of the anal squeeze pressure increment.ConclusionsPatients with anorectal disorders commonly have a patulous anal canal, which is associated with more severe anal injury and independently predicted anal resting pressure and squeeze pressure increment. It therefore is important to identify a patulous anal canal because it appears to be a marker of not only anal sphincter injury but disturbances beyond sphincter injury, such as damage to the anal cushions or anal denervation.

Project description:BackgroundIncidence of complications following obstetrical anal sphincter injury (OASI) during vaginal delivery are poorly defined. They are only studied in high level maternities, small cohorts, all stages of perineal tear or in low-income countries. The aim of our study was to describe complications after primary OASI repair following a vaginal delivery in all French maternity wards at short and midterm and to assess factors associated with complication occurrence.MethodsWe conducted a historical cohort study using the French nationwide claim database (PMSI) from January 2013 to December 2021. All women who sustained an OASI repair following a vaginal delivery were included and virtually followed-up for 2 years. Then, we searched for OASIS complications. Finally, we evaluated factors associated with OASIS complication repaired or not and OASIS complication repairs.ResultsAmong the 61,833 included women, 2015 (2.8%) had an OASI complication and 842 (1.16%) underwent an OASI complication repair. Women were mainly primiparous (71.6%) and 44.3% underwent an instrumental delivery. During a follow-up of 2 years, 0.6% (n = 463), 0.3% (n = 240), 0.2% (n = 176), 0.1% (n = 84), 0.06% (n = 43) and 0.01% (n = 5) of patients underwent second surgery for a perineal repair, a fistula repair, a sphincteroplasty, a perineal infection, a colostomy and a sacral nervous anal stimulation, respectively. Only one case of artificial anal sphincter was noticed. Instrumental deliveries (OR = 1.56 CI95%[1.29;1.9]), private for-profit hospitals (OR = 1.42 [1.11;1.82], reference group "public hospital"), obesity (OR = 1.36 [1;1.84]), stage IV OASIS (OR = 2.98 [2.4;3.72]), perineal wound breakdown (OR = 2.8 [1.4;5.48]), ages between 25 and 29 years old (OR = 1.59 [1.17;2.18], refence group "age between 13 and 24 years old") and 30 and 34 years old (OR = 1.57 [1.14; 2.16], refence group "age between 13 and 24 years old") were factors associated with OASIS complication repairs.ConclusionsMaternal age, stage IV OASIS, obesity, instrumental deliveries and private for-profit hospitals seemed to predict OASIS complications. Understanding factors associated with OASIS complications could be beneficial for the patient to inform them and to influence the patient's follow-up in order to prevent complications, repairs and maternal distress.

Dataset Information

Functional Outcome of Human Adipose Stem Cell Injections in Rat Anal Sphincter Acute Injury Model.

Publications

Functional Outcome of Human Adipose Stem Cell Injections in Rat Anal Sphincter Acute Injury Model.

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