Cell Therapy for Anal Sphincter Incontinence: Where Do We Stand?

Abstract

Anal sphincter incontinence is a chronic disease, which dramatically impairs quality of life and induces high costs for the society. Surgery, considered as the best curative option, shows a disappointing success rate. Stem/progenitor cell therapy is pledging, for anal sphincter incontinence, a substitute to surgery with higher efficacy. However, the published literature is disparate. Our aim was to perform a review on the development of cell therapy for anal sphincter incontinence with critical analyses of its pitfalls. Animal models for anal sphincter incontinence were varied and tried to reproduce distinct clinical situations (acute injury or healed injury with or without surgical reconstruction) but were limited by anatomical considerations. Cell preparations used for treatment, originated, in order of frequency, from skeletal muscle, bone marrow or fat tissue. The characterization of these preparations was often incomplete and stemness not always addressed. Despite a lack of understanding of sphincter healing processes and the exact mechanism of action of cell preparations, this treatment was evaluated in 83 incontinent patients, reporting encouraging results. However, further development is necessary to establish the correct indications, to determine the most-suited cell type, to standardize the cell preparation method and to validate the route and number of cell delivery.

The Effect of Mesenchymal Stem Cells, Adipose Tissue Derived Stem Cells, and Cellular Stromal Vascular Fraction on the Repair of Acute Anal Sphincter Injury in Rats

“…In our study, on day 5, the incisions in the PBS injection group were close to healing. Comparing with previous 25% anal sphincterectomy studies by others at adjacent time points [ 14 , 17 , 44 ], it appeared that the rats in our modeling showed faster healing and tissue sectioning. This may first be due to differences in observation time.…”

“…MSC can be derived from various sources [ 10 ] with differences in marker expression profile and differentiation potential [ 11 ]. To date, MSC [ 12 , 13 , 14 ], adipose-derived stem cells (ADSC) [ 15 ], and skeletal muscle-derived stem cells [ 16 ] have been used in preclinical and clinical studies over the past few years [ 17 , 18 , 19 ] and have shown significant therapeutic effects in treating ASI. Williams et al [ 20 ] treated intrinsic urinary sphincter deficiency (ISD) with skeletal muscle precursor stem cells and showed improvement in muscle proportions and urethral function, and the local injection group showed better efficacy than the intravenous injection group.…”

Sacral and Percutaneous Tibial Nerve Stimulation, Stem Cell Therapy, and Transanal Irrigation Device

“…In 44 studies, MSCs originated from muscle in 28 studies (17 skeletal and 11 smooth), from BM in 10, and from AT in 6. Eight studies used neural cells for bioengineered constructs and one publication used umbilical cord [24].…”

Isolation and Characterization of Stem Cells from the Anal Canal Transition Zone in Pigs

“…Stem cell therapy is a promising approach to cure degenerative diseases and has been proposed for the treatment of various disease, including anal sphincter incontinence (ASI) [1][2][3]. Despite more than 20 years of research in this field with encouraging preclinical studies and clinical trials, there still is a lack of consensus regarding the cells that should be used [1][2][3][4]. In the literature, two candidates emerged for clinical application: muscular tissue-derived stem cells (M-SCs) (satellite cells or myoblasts) and adipose-tissue derived stem cells (A-SCs) [3].…”