Safety and Efficacy of Iltamiocel Cellular Therapy for the Treatment of Fecal Incontinence. Results of a Phase 1/2 Study.

Objective: To examine the safety and efficacy of iltamiocel, an investigational cellular therapy of autologous muscle-derived cells, as a treatment for fecal incontinence (FI) in adults.

Background: Limited therapeutic options are available for patients with FI refractory to conservative treatments. Cell therapy using autologous muscle-derived cells represents a promising, minimally invasive approach for restoring anal sphincter function.

Autologous Muscle-Derived Cell Therapy for Swallowing Impairment in Patients Following Treatment for Head and Neck Cancer.

Objectives/hypothesis: To evaluate the safety and potential efficacy of autologous muscle-derived cells (AMDCs) for the treatment of swallowing impairment following treatment for oropharynx cancer.

Study Design: Prospective, phase I, open label, clinical trial.

Methods: Oropharynx cancer survivors disease free ≥2 years post chemoradiation were recruited.

A double-blind, randomized, placebo-controlled clinical trial evaluating the safety and efficacy of autologous muscle derived cells in female subjects with stress urinary incontinence.

Purpose: The purpose of the study was to assess safety and efficacy of autologous muscle derived cells for urinary sphincter repair (AMDC-USR) in female subjects with predominant stress urinary incontinence.

Methods: A randomized, double-blind, multicenter trial examined intra-sphincteric injection of 150 × 10 AMDC-USR versus placebo in female subjects with stress or stress predominant, mixed urinary incontinence. AMDC-USR products were generated from vastus lateralis needle biopsies.

Human skeletal muscle cells with a slow adhesion rate after isolation and an enhanced stress resistance improve function of ischemic hearts.

Identification of cells that are endowed with maximum potency could be critical for the clinical success of cell-based therapies. We investigated whether cells with an enhanced efficacy for cardiac cell therapy could be enriched from adult human skeletal muscle on the basis of their adhesion properties to tissue culture flasks following tissue dissociation. Cells that adhered slowly displayed greater myogenic purity and more readily differentiated into myotubes in vitro than rapidly adhering cells (RACs).

Endoscopic injection of skeletal muscle-derived cells augments gut smooth muscle sphincter function: implications for a novel therapeutic approach.

Introduction: Sphincter function is a common problem in gastroenterology and leads to disorders such as GERD and fecal incontinence.

Objective: We hypothesized that transplantation of skeletal muscle-derived cells (MDCs) into GI sphincters may improve their function, leading to a more physiological approach to treating these disorders.

Design: We performed experiments to test the potential of MDCs to survive and differentiate within the GI smooth muscle in order to gain further knowledge on the biology of skeletal muscle transplantation in GI smooth muscle sphincters as well as to test the safety and feasibility of endoscopic injection of MDCs in a large animal model.

In vitro and in vivo effect of lidocaine on rat muscle-derived cells for treatment of stress urinary incontinence.

Objectives: Lidocaine cytotoxicity has been reported in some cell types, which could affect its use as a local anesthetic in cell-based therapy. We evaluated the in vitro and in vivo effect of lidocaine on rat muscle-derived progenitor cells (MDCs).

Methods: MDCs were isolated from rat skeletal muscle and purified using the preplate technique.

Physiological effects of human muscle-derived stem cell implantation on urethral smooth muscle function.

The physiological effects of human muscle-derived stem cell (MDSC) implantation on urethral smooth muscle function were investigated in pudendal nerve-transected nude rats with human MDSC (TM) or saline (TS) injection into the proximal urethra compared with sham-operated, saline-injected nude rats (SS). Leak point pressure (LPP) before and after hexamethonium application, which can block autonomic efferent nerves, and proximal urethral contractile responses to carbachol and phenylephrine in muscle strip study were examined 6 weeks after the implantation. There was no significant difference between the LPPs in SS and TM.

The potential of muscle-derived stem cells for stress urinary incontinence.

The suburethral sling procedures, such as transvaginal tape (TVT), have recently gained popularity for the treatment of stress urinary incontinence (SUI). This TVT procedure can reinforce the weakness of pelvic floor muscles but urethral sphincter deficiency remains. Adult stem cell injection therapy for SUI has recently been at the forefront of the repair of deficient urethral function.

The promise of stem cell therapy to restore urethral sphincter function.

The promise of stem cell therapy for the treatment of stress urinary incontinence is that transplanted stem cells may undergo self-renewal and potential multipotent differentiation, leading to urethral sphincter regeneration. Cell-based therapies are most often associated with the use of autologous multipotent stem cells, such as bone marrow cells. However, harvesting bone marrow stromal stem cells is difficult, painful, and may yield low numbers of stem cells.

Human muscle-derived cell injection in a rat model of stress urinary incontinence.

We investigated the use of human muscle-derived cells (hMDCs) for the treatment of stress urinary incontinence (SUI) in a nude rat model. hMDCs were isolated from adult skeletal muscle. Three groups of six animals consisting of controls, animals undergoing sciatic nerve transection (SNT) with periurethral sham-injection, and SNT with hMDCs (1 x 10(6) cells/20 microl saline) were utilized.

State of the art of where we are at using stem cells for stress urinary incontinence.

Aims: This review aims to discuss: 1) the neurophysiology, highlighting the importance of the middle urethra, and treatment of stress urinary incontinence (SUI); 2) current injectable cell sources for minimally-invasive treatment; and 3) the potential of muscle-derived stem cells (MDSCs) for the delivery of neurotrophic factors.

Methods: A PUB-MED search was conducted using combinations of heading terms: urinary incontinence, urethral sphincter, stem cells, muscle, adipose, neurotrophins. In addition, we will update the recent work from our laboratory.

Ex vivo biomechanical properties of the female urethra in a rat model of birth trauma.

Stress urinary incontinence (SUI) is the involuntary release of urine during sudden increases in abdominal pressures. SUI is common in women after vaginal delivery or pelvic trauma and may alter the biomechanical properties of the urethra. Thus we hypothesize that injury due to vaginal distension (VD) decreases urethral basal tone and passive stiffness.

Biomechanical characterization of the urethral musculature.

Rigorous study of the associations between urethral structural anatomy and biomechanical function is necessary to advance the understanding of the development, progression, and treatment of urethral pathologies. An ex vivo model was utilized to define the relative biomechanical contributions of the active (muscle) elements of the female urethra relative to its passive (noncontractile) elements. Whole urethras from female, adult rats were tested under a range of applied intraluminal pressures (0 to 20 mmHg) as a laser micrometer simultaneously measured midurethral outer diameter.

Establishing reliable criteria for isolating myogenic cell fractions with stem cell properties and enhanced regenerative capacity.

Despite a focused effort within the myogenic cell transplantation community, little progress has been made toward the reliable identification and isolation of progenitors that are capable of tolerating the initial posttransplantation environment and effectively regenerating clinically relevant quantities of muscle. The future success of myogenic-based treatment modalities requires an enhanced understanding of the highly heterogeneous nature of the myogenic progenitor cell pool, which has been previously documented by numerous researchers. Further, for translation of experimental animal results to clinical application, reliable in vitro selection criteria must be established and must be translatable across species.

Development of an experimental system for the study of urethral biomechanical function.

Despite its principal mechanical function in the storage and release of urine, the biomechanical properties of the urethra have remained largely unexplored. The purpose of this study was to develop and validate an experimental model that can be used for evaluating whole urethral tissue in such a manner. Bladder-urethral specimens were excised from halothane-anesthetized female rats and mounted at in vivo length within the experimental apparatus consisting of a tissue perfusion chamber, an adjustable fluid column, and a laser micrometer.

Muscle stem cells differentiate into haematopoietic lineages but retain myogenic potential.

Muscle-derived stem cells (MDSCs) can differentiate into multiple lineages, including haematopoietic lineages. However, it is unknown whether MDSCs preserve their myogenic potential after differentiation into other lineages. To address this issue, we isolated from dystrophic muscle a population of MDSCs that express stem-cell markers and can differentiate into various lineages.

The role of CD34 expression and cellular fusion in the regeneration capacity of myogenic progenitor cells.

Characterization of myogenic subpopulations has traditionally been performed independently of their functional performance following transplantation. Using the preplate technique, which separates cells based on their variable adhesion characteristics, we investigated the use of cell surface proteins to potentially identify progenitors with enhanced regeneration capabilities. Based on previous studies, we used cell sorting to investigate stem cell antigen-1 (Sca-1) and CD34 expression on myogenic populations with late adhesion characteristics.