Perspective: autologous skeletal muscle cells for the treatment of fecal incontinence.

Abstract

Fecal incontinence afflicts a substantial percentage of the population and increases in frequency with advancing age. While physicians and surgeons have developed an array of noninvasive and surgical approaches to this disorder, for many patients it remains a chronic condition that has considerable impact on quality of life and socialization. Consequently, investigators have continued to seek out novel therapeutic approaches. In the current issue of Techniques in Coloproctology, Romaniszyn et al. [1] describe a regenerative surgical approach to fecal incontinence. They designed their study based in part on (a) a preclinical rat model reporting that the injection of bone marrow-derived mesenchymal stem cells (MSC), also known as multipotent stromal cells [2], (b) quantitatively improved objective measures of fecal incontinence [3, 4]; and (c) a pilot clinical study by Frudinger et al. [5] reporting that women with fecal incontinence showed objective improvement in rectal function for up to 1 year following injection of skeletal muscle-derived cells. Here, Romaniszyn et al. [1] report positive outcomes in a pilot study treating fecal incontinence with autologous skeletal muscle cell injection. The authors enrolled ten patients (nine females and one male) with severe fecal incontinence that had persisted despite 6 months of conventional biofeedback therapy. Each patient underwent harvesting of 1 cc of skeletal muscle which was used to isolate and culture expand autologous skeletal muscle cells over a 5to 6-week period. At a subsequent visit, the patient’s own skeletal muscle cells were injected into the rectal sphincter with ultrasound guidance. The patients were followed for up to 12 months using quantitative and qualitative outcome measures. One of the ten patients was lost to follow up during the study period. By 18 weeks of follow-up, twothirds of the patients (n = 6) reported subjective improvement in symptoms and over half had improved quantitative parameters of rectal function; however, after 1 year of follow-up, two of these patients exhibited a decline in both their qualitative and quantitative improvements [1]. This report by Romaniszyn et al. [1] is among the first to independently confirm the clinical observations from Frudinger et al. [5]. Romaniszyn et al.’s findings are particularly timely since Frudinger et al. [6] just published a follow-up to their original clinical cohort documenting persistent improvements in patient symptoms for up to 5 years [6]. Multipotent stromal/stem cells can be isolated from skeletal muscle, bone marrow, and adipose tissue [7]. Due to their relatively easy access in most adults, preclinical and clinical studies exploring the use of autologous and allogeneic cell-based therapies have increased exponentially over the past two decades [8, 9]. The US National Institutes of Health tracks the number of registered clinical trials, and their Web site (www.clinicaltrials.gov) offers a snap shot of the clinical landscape. A recent search of the Web site identifies 298 studies associated with ‘‘mesenchymal stem cells’’ and 159 associated with ‘‘skeletal muscle cells.’’ These studies are conducted routinely by academia, government agencies, industry, and combinations thereof. In recent years, regulatory agencies such as the FDA and EMEA have substantially expanded their inhouse expertise for the quantitative assessment cell-based & J. M. Gimble jgimble@tulane.edu