In Vivo Recovery of the Injured Anal Sphincter After Repair and Injection of Myogenic Stem Cells

Lane, Felicia; Jacobs, Stephanie; Craig, Jocelyn B.; Nistor, Gabriel; Markle, Danielle; Noblett, Karen; Osann, Kathryn; Keirstead, Hans S.

doi:10.1097/dcr.0b013e3182a4adfb

Cited by 21 publications

(19 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study, the anal pressures were comparable with the other animal studies although there are slight variations—possibly due to different techniques (balloon vs. double‐triple‐lumen‐catheter, electrical stimulation vs. spontaneous contraction) and different size of the anal canal in different species 13, 16, 19. Salcedo et al stated that rat anal pressures tend to return to baseline after sphincterotomy at 4 weeks even without intervention, but this does not occur after pudendal nerve transection 42.…”

Section: Discussionsupporting

confidence: 84%

“…It has been suggested that stem cell transplantation may facilitate endogenous repair even in patients with advanced age and comorbidities who have compromised repair function [13]. Therefore, stem cell therapy would be especially useful in patients with compromised anal sphincter function.…”

Section: Discussionmentioning

confidence: 99%

“…There are several studies concerning stem cells in the treatment of anal sphincter defects. Rat models with muscle-derived stem cells or myoblasts as the stem cell origin are the most common study designs [10][11][12][13][14], although bigger animals (rabbits, dogs) have been used as well [15,16]. Mesenchymal stem cells (MSC) derived from bone marrow have been used in a few studies and the results are promising [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Kuismanen

Juntunen

Narra

et al. 2018

Stem Cells Translational Medicine

View full text Add to dashboard Cite

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 μl) 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 (μCT) 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 μCT 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 μCT image data lends greater confidence in assessing muscle healing and continuity. Stem Cells Translational Medicine 2018;7:295–304

show abstract

Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Kuismanen

Juntunen

Narra

et al. 2018

Stem Cells Translational Medicine

View full text Add to dashboard Cite

show abstract

“…We decided to use the anesthetic ketamine/xylazine mixture, because it was the one we found to provide more stable registries. This mixture was also used by Zutshi and colleagues[ 29 , 34 - 36 ], but other authors have employed ketamine with better results than ours[ 37 ].…”

Section: Discussionmentioning

confidence: 89%

Rat model of anal sphincter injury and two approaches for stem cell administration

Trébol¹,

Georgiev-Hristov²,

Vega-Clemente³

et al. 2018

WJSC

View full text Add to dashboard Cite

AIMTo establish a rat model of anal sphincter injury and test different systems to provide stem cells to injured area.METHODSAdipose-derived stem cells (ASCs) were isolated from BDIX rats and were transfected with green fluorescent protein (GFP) for cell tracking. Biosutures (sutures covered with ASCs) were prepared with 1.5 x 106 GFP-ASCs, and solutions of 106 GFP-ASCs in normal saline were prepared for injection. Anorectal normal anatomy was studied on Wistar and BDIX female rats. Then, we designed an anal sphincter injury model consisting of a 1-cm extra-mucosal miotomy beginning at the anal verge in the anterior middle line. The sphincter lesion was confirmed with conventional histology (hematoxylin and eosin) and immunofluorescence with 4', 6-diamidino-2-phenylindole (commonly known as DAPI), GFP and α-actin. Functional effect was assessed with basal anal manometry, prior to and after injury. After sphincter damage, 36 BDIX rats were randomized to three groups for: (1) Cell injection without repair; (2) biosuture repair; and (3) conventional suture repair and cell injection. Functional and safety studies were conducted on all the animals. Rats were sacrificed after 1, 4 or 7 d. Then, histological and immunofluorescence studies were performed on the surgical area.RESULTSWith the described protocol, biosutures had been covered with at least 820000-860000 ASCs, with 100% viability. Our studies demonstrated that some ASCs remained adhered after suture passage through the muscle. Morphological assessment showed that the rat anal anatomy is comparable with human anatomy; two sphincters are present, but the external sphincter is poorly developed. Anal sphincter pressure data showed spontaneous, consistent, rhythmic anal contractions, taking the form of “plateaus” with multiple twitches (peaks) in each pressure wave. These basal contractions were very heterogeneous; their frequency was 0.91-4.17 per min (mean 1.6980, SD 0.57698), their mean duration was 26.67 s and mean number of peaks was 12.53. Our morphological assessment revealed that with the aforementioned surgical procedure, both sphincters were completely sectioned. In manometry, the described activity disappeared and was replaced by a gentle oscillation of basal line, without a recognizable pattern. Surprisingly, these findings appeared irrespective of injury repair or not. ASCs survived in this potentially septic area for 7 d, at least. We were able to identify them in 84% of animals, mainly in the muscular section area or in the tissue between the muscular endings. ASCs formed a kind of “conglomerate” in rats treated with injections, while in the biosuture group, they wrapped the suture. ASCs were also able to migrate to the damaged zone. No relevant adverse events or mortality could be related to the stem cells in our study. We also did not find unexpected tissue growths.CONCLUSIONThe proposed procedure produces a consistent sphincter lesion. Biosutures and injections are suitable for cell delivery. ASCs survive and are completely safe in this clinical s...

show abstract

“…The exact mechanisms, histomorphologic and functional changes of disrupted sphincter muscles in response to myoblasts, are being studied using animal models. [121-123] In humans, similar regenerative therapy with autologous cells injected into the urethral sphincter in patients with stress urinary incontinence appears to be beneficial in small investigational studies. [124,125] The pilot study has been conducted to evaluate the clinical efficacy of the autologous myoblast cell injection (cultured and harvested from the pectoralis muscle) in women with symptomatic FI due to disrupted EAS from obstetric trauma.…”

Section: Investigational Treatment Optionsmentioning

confidence: 99%

Evidence-Based Update on Treatments of Fecal Incontinence in Women

Meyer

Richter

2016

Obstetrics and Gynecology Clinics of North America

View full text Add to dashboard Cite

Synopsis Fecal incontinence is a highly prevalent and distressing condition which negatively impacts quality of life. The etiology is often multifactorial, and the evaluation and treatment of this condition can be hindered by a lack of understanding of the mechanisms and currently available treatment options. This article will review the evidence-based update for the management of fecal incontinence.

show abstract

In Vivo Recovery of the Injured Anal Sphincter After Repair and Injection of Myogenic Stem Cells

Cited by 21 publications

References 17 publications

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

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

Rat model of anal sphincter injury and two approaches for stem cell administration

Evidence-Based Update on Treatments of Fecal Incontinence in Women

Contact Info

Product

Resources

About