Effect of Myogenic Stem Cells on Contractile Properties of the Repaired and Unrepaired Transected External Anal Sphincter in an Animal Model

White, Amanda B.; Keller, Patrick W.; Acevedo, Jesús F.; Word, R. Ann; Wai, Clifford Y.

doi:10.1097/aog.0b013e3181d56cc5

Cited by 39 publications

(47 citation statements)

References 28 publications

(25 reference statements)

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“…Previous functional anal sphincter assessments have mostly been performed in vitro using anal sphincter muscle samples from euthanized animals to measure the contractility after electrical stimulation 10, 12, 17, 37. Salcedo et al measured in vivo function of the anal sphincter after a sphincterotomy or pudendal nerve crush followed by either rat bone‐marrow derived MSC injection or saline 18.…”

Section: Discussionmentioning

confidence: 99%

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

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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

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Section: Discussionmentioning

confidence: 99%

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

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“…Several animal studies have been reported on anal sphincter dysfunction induced by surgical techniques (18)(19)(20)(21)(22)(23). For instance, Salcedo, et al (20) investigated two different models of anal sphincter dysfunction (i.e., sphincterotomy and bilateral pudendal nerve transection) in rodents.…”

Section: Discussionmentioning

confidence: 99%

“…However, these 7 7 studies were based on the hypotheses that these models had complete fecal incontinence. Since then, several conventional anal dysfunction animal models were reported, such as the sphincterotomy model (19)(20)(21)(22), cryoinjured anal sphincter model (23) and pudendal nerve transection model (19,20).…”

Section: Introductionmentioning

confidence: 99%

A novel animal model of long-term sustainable anal sphincter dysfunction

Yamaguchi

Fujita

Yamanouchi

et al. 2013

Journal of Surgical Research

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“…This enabled achievement of histologically proven destruction of one sector of the anal sphincter, provoking a significant decrease in contractile force. We preferred this approach to sphincterotomy (1,12,19,35), since it is not only more convenient to perform but also less traumatic for the rat.…”

Section: Discussionmentioning

confidence: 99%

“…Hence, among the few experimental studies of myoblast anal sphincter injection, this is the first report of a longitudinal functional study in individual animals (12,13,35). To achieve myoblast tracking, injected cells were transduced with a GFP-encoding lentiviral vector.…”

Section: Myoblast Cell Therapy In Fecal Incontinencementioning

confidence: 99%

Restoration of Anal Sphincter Function after Myoblast Cell Therapy in Incontinent Rats

et al. 2015

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Fecal incontinence (FI) remains a socially isolating condition with profound impact on quality of life for which autologous myoblast cell therapy represents an attractive treatment option. We developed an animal model of FI and investigated the possibility of improving sphincter function by intrasphincteric injection of syngeneic myoblasts. Several types of anal cryoinjuries were evaluated on anesthetized Fischer rats receiving analgesics. The minimal lesion yielding sustainable anal sphincter deficiency was a 90°cryoinjury of the sphincter, repeated after a 24-h interval. Anal sphincter pressure was evaluated longitudinally by anorectal manometry under local electrostimulation. Myoblasts were prepared using a protocol mimicking a clinical-grade process and further transduced with a GFP-encoding lentiviral vector before intrasphincteric injection. Experimental groups were uninjured controls, cryoinjured + PBS, and cryoinjured + myoblasts (different doses or injection site). Myoblast injection was well tolerated. Transferred myoblasts expressing GFP integrated into the sphincter and differentiated in situ into dystrophin-positive mature myofibers. Posttreatment sphincter pressures increased over time. At day 60, pressures in the treated group were significantly higher than those of PBS-injected controls and not significantly different from those of normal rats. Longitudinal follow-up showed stability of the therapeutic effect on sphincter function over a period of 6 months. Intrasphincteric myoblast injections at the lesion borders were equally as effective as intralesion administration, but an injection opposite to the lesion was not. These results provide proof of principle for myoblast cell therapy to treat FI in a rat model. This strategy is currently being evaluated in humans in a randomized double-blind placebo-controlled clinical trial.

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Effect of Myogenic Stem Cells on Contractile Properties of the Repaired and Unrepaired Transected External Anal Sphincter in an Animal Model

Cited by 39 publications

References 28 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

A novel animal model of long-term sustainable anal sphincter dysfunction

Restoration of Anal Sphincter Function after Myoblast Cell Therapy in Incontinent Rats

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