Mesenchymal stem cells can improve anal pressures after anal sphincter injury

Abstract

Objective Fecal incontinence reduces the quality of life of many women but has no long-term cure. Research on mesenchymal stem cell (MSC)-based therapies has shown promising results. The primary aim of this study was to evaluate functional recovery after treatment with MSCs in two animal models of anal sphincter injury. Methods Seventy virgin female rats received a sphincterotomy (SP) to model episiotomy, a pudendal nerve crush (PNC) to model the nerve injuries of childbirth, a sham SP, or a sham PNC. Anal sphincter pressures and electromyography (EMG) were recorded after injury but before treatment and 10 days after injury. Twenty-four hours after injury, each animal received either 0.2 ml saline or 2 million MSCs labelled with green fluorescing protein (GFP) suspended in 0.2 ml saline, either intravenously (IV) into the tail vein or intramuscularly (IM) into the anal sphincter. Results MSCs delivered IV after SP resulted in a significant increase in resting anal sphincter pressure and peak pressure, as well as anal sphincter EMG amplitude and frequency 10 days after injury. MSCs delivered IM after SP resulted in a significant increase in resting anal sphincter pressure and anal sphincter EMG frequency but not amplitude. There was no improvement in anal sphincter pressure or EMG with in animals receiving MSCs after PNC. GFP-labelled cells were not found near the external anal sphincter in MSC-treated animals after SP. Conclusion MSC treatment resulted in significant improvement in anal pressures after SP but not after PNC, suggesting that MSCs could be utilized to facilitate recovery after anal sphincter injury.

Functional Outcome After Anal Sphincter Injury and Treatment With Mesenchymal Stem Cells

“…or over time have shown improved outcomes in the heart [44] and in diabetes [45] in animal models. In our preliminary study [38], we demonstrated that i.v. infusions had a better effect than i.m.…”

“…We also showed that the improvement in anal sphincter pressures was higher when the MSCs were delivered i.v. [38]. We studied the process of homing because in clinical practice fecal incontinence manifests many years after the acute injury and may be affected by other factors such as surgery, radiation, change in bowel habits, and aging muscles, which compound the symptoms.…”

“…Cell culturing was done as previously described [38]. Virgin female Sprague-Dawley rats were euthanized and bone marrow was harvested from the tibia and femurs by gently flushing the bone with 1 ml Dulbecco's modified Eagle's medium (DMEM; Invitrogen, Carlsbad, CA, http://www.invitrogen.com).…”

“…In the anal sphincter, the effect of MSCs has been studied, although most of the studies have used ex vivo outcome testing [32][33][34][35][36][37]. In a prior preliminary study [38], we determined the effect of intramuscular and intravenous injection of bone marrow-derived MSCs on anal sphincter pressures after anal sphincter injury or pudendal nerve crush. Our results showed improvement in resting and peak pressures after both i.m.…”

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

“…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. In their further investigations, the same research group found that both serial i.v.…”