Muscle-derived cell injection to treat anal incontinence due to obstetric trauma: pilot study with 1 year follow-up

Frudinger, Andrea; Kölle, D.; Schwaiger, Wolfgang; Pfeifer, Johann; Paede, J.; Halligan, Steve

doi:10.1136/gut.2009.181347

Cited by 122 publications

(140 citation statements)

References 36 publications

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“…3 Urethral sphincter deficiency resulting in incontinence is a condition that is also likely to benefit from this type of therapy. [4][5][6][7][8] Smooth muscle provides an important function for a number of physiological processes. This includes, for example, peristaltic movements within the gastrointestinal tract, 9 regulation of blood pressure, 10 and maintaining ventilation of the airways.…”

Section: Introductionmentioning

confidence: 99%

A Novel Method for Differentiation of Human Mesenchymal Stem Cells into Smooth Muscle-Like Cells on Clinically Deliverable Thermally Induced Phase Separation Microspheres

Parmar

Ahmadi²,

Day³

2015

Tissue Engineering Part C: Methods

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Muscle degeneration is a prevalent disease, particularly in aging societies where it has a huge impact on quality of life and incurs colossal health costs. Suitable donor sources of smooth muscle cells are limited and minimally invasive therapeutic approaches are sought that will augment muscle volume by delivering cells to damaged or degenerated areas of muscle. For the first time, we report the use of highly porous microcarriers produced using thermally induced phase separation (TIPS) to expand and differentiate adipose-derived mesenchymal stem cells (AdMSCs) into smooth muscle-like cells in a format that requires minimal manipulation before clinical delivery. AdMSCs readily attached to the surface of TIPS microcarriers and proliferated while maintained in suspension culture for 12 days. Switching the incubation medium to a differentiation medium containing 2 ng/ mL transforming growth factor beta-1 resulted in a significant increase in both the mRNA and protein expression of cell contractile apparatus components caldesmon, calponin, and myosin heavy chains, indicative of a smooth muscle cell-like phenotype. Growth of smooth muscle cells on the surface of the microcarriers caused no change to the integrity of the polymer microspheres making them suitable for a cell-delivery vehicle. Our results indicate that TIPS microspheres provide an ideal substrate for the expansion and differentiation of AdMSCs into smooth muscle-like cells as well as a microcarrier delivery vehicle for the attached cells ready for therapeutic applications.

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Section: Introductionmentioning

confidence: 99%

A Novel Method for Differentiation of Human Mesenchymal Stem Cells into Smooth Muscle-Like Cells on Clinically Deliverable Thermally Induced Phase Separation Microspheres

Parmar

Ahmadi²,

Day³

2015

Tissue Engineering Part C: Methods

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“…Frudinger et al treated 10 patients with autologous myogenic stem cells and found a significant improvement in the AI symptoms at 1‐ and 5‐year controls. However, there was no significant change in anal manometry measurements 39, 40. In a small pilot study, where hASCs therapy was used in combination with surgical sphincteroplasty in treatment of AI, there was no difference in AI symptoms between the hASC and saline injection group.…”

Section: Discussionmentioning

confidence: 85%

“…To simplify the cell isolation and proliferation process, Mazzanti et al used freshly isolated minimally manipulated bone‐marrow derived mononuclear cells without expansion and found them to be as effective as in vitro expanded BM‐MSCs in the recovery of iatrogenic anal sphincter rupture 38. Muscle‐derived stem cell injections have been used in small pilot studies in women and the results are promising 39, 40, 41. Frudinger et al treated 10 patients with autologous myogenic stem cells and found a significant improvement in the AI symptoms at 1‐ and 5‐year controls.…”

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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“…Studies show promising results with improvement in FI symptoms and low complication rates. 15 In conclusion, fecal incontinence is an overlooked, underreported debilitating condition; medical practitioners must be comfortable with its evaluation and management. The most important aspect of the initial workup is obtaining a thorough history.…”

Section: Treatment: Nonoperativementioning

confidence: 99%

Fecal Incontinence: Etiology, Evaluation, and Treatment

Hayden

Weiss

2011

Clinics in Colon and Rectal Surgery

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Fecal incontinence is a debilitating problem facing 2.2% of the U.S. general population over 65 years of age. Etiologic factors include traumatic, neurologic, congenital, and iatrogenic. Most commonly, obstetric trauma causes fecal incontinence as well as poorly performed anorectal surgery or pelvic radiation. Several severity scores and quality of life indexes have been developed to quantify incontinent symptoms. There are several nonsurgical and surgical options for the treatment of fecal incontinence. Biofeedback is among the most successful nonoperative strategies. Depending on the cause, anal sphincter repair, artificial bowel sphincter, and sacral nerve stimulation are used to treat fecal incontinence with some success. Unfortunately, fecal incontinence is an extremely difficult problem to manage: there has not been one, single treatment option that has proven to be both safe and effective in long-term studies.KEYWORDS: Fecal incontinence, anal sphincter repair, sacral nerve stimulation, artificial bowel sphincter, biofeedbackObjectives: On completion of this article, the reader should be able to summarize the causes and treatment options of fecal incontinence, including both surgical and nonoperative. BACKGROUNDFecal incontinence (FI) is a debilitating and embarrassing problem facing 2.2% of the U.S. general population over 65 years old. 1 This disorder is more prevalent in the elderly population and is one of the most common reasons for nursing home placement. 2,3 The etiology of FI is multifactorial and can be due to several factors including neuropathic, traumatic, congenital, and obstetric trauma, as well as iatrogenic injuries due to injudicious fistula surgery, hemorrhoidectomy, and lateral internal sphincterotomy among several others. FI symptoms can range from mild to severe and the work-up and treatments of this disorder are just as varied. Patients may complain of incontinence to flatus,

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Muscle-derived cell injection to treat anal incontinence due to obstetric trauma: pilot study with 1 year follow-up

Abstract: Injection of autologous myoblasts is safe, well tolerated, and significantly improves symptoms of anal incontinence due to obstetric anal sphincter trauma.

Cited by 122 publications

References 36 publications

A Novel Method for Differentiation of Human Mesenchymal Stem Cells into Smooth Muscle-Like Cells on Clinically Deliverable Thermally Induced Phase Separation Microspheres

A Novel Method for Differentiation of Human Mesenchymal Stem Cells into Smooth Muscle-Like Cells on Clinically Deliverable Thermally Induced Phase Separation Microspheres

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

Fecal Incontinence: Etiology, Evaluation, and Treatment

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