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.

New technology assessment and current and upcoming therapies for underactive bladder.

Background And Aims: Stakeholders from around the world came together to address the unmet needs of underactive bladder (UAB) at the 3rd International Congress for Underactive Bladder.

Methods: The main recommendation from the regulatory working group is a need for a meeting of UAB stakeholders and regulatory agencies including the FDA to discuss guidance for regulatory trial design for devices, drugs, and/or biologics for UAB.

Results: The following issues to be discussed and agreed upon for UAB trials: 1) Appropriate inclusion and exclusion criteria.

Intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder: pilot study.

We conducted the first-regenerative medicine cellular therapy for underactive bladder (UAB) in an FDA-approved, compassionate-use IND trial to evaluate treatment safety and potential clinical efficacy of autologous muscle-derived stem cells (AMDC) on a patient with UAB. No study-related adverse events or side effects were reported. In the 1-year follow-up period, the subject denied any gross hematuria, urgency, frequency or infection.

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.

Advances toward tissue engineering for the treatment of stress urinary incontinence.

Suburethral pubovaginal sling placement is a common surgical procedure for the treatment of stress urinary incontinence. A wide variety of graft materials is available, each associated with inherent desirable and undesirable characteristics and complications. In this article, we discuss the rationale for and application of small intestinal submucosa (SIS) in lower urinary tract tissue engineering, with emphasis on the use of SIS as a suitable and biologically compatible sling material.

Periurethral cellular injection: comparison of muscle-derived progenitor cells and fibroblasts with regard to efficacy and tissue contractility in an animal model of stress urinary incontinence.

Objectives: To compare muscle-derived cells (MDCs) and fibroblasts with regard to their potential for restoration of urethral function on injection in a previously established animal model of stress urinary incontinence.

Methods: The animals were divided into four (dosage) or five (cell concentration) experimental groups: normal, nontreated controls (normal group) or bilateral sciatic nerve transection with either periurethral injection of saline (saline group), MDCs (MDC group), fibroblasts (fibroblast group), or MDC/fibroblast mixture (mixed group). At 4 weeks after injection, the leak point pressure (LPP) was measured and contractility testing and histologic analysis were performed.

Biaxial mechanical properties of muscle-derived cell seeded small intestinal submucosa for bladder wall reconstitution.

Bladder wall replacement remains a challenging problem for urological surgery due to leakage, infection, stone formation, and extensive time needed for tissue regeneration. To explore the feasibility of producing a more functional biomaterial for bladder reconstitution, we incorporated muscle-derived cells (MDC) into small intestinal submucosa (SIS) scaffolds. MDC were harvested from mice hindleg muscle, transfected with a plasmid encoding for beta-galactosidase, and placed into single-layer SIS cell culture inserts.

Exercise training increases intramyocellular lipid and oxidative capacity in older adults.

Intramyocellular lipid (IMCL) has been associated with insulin resistance. However, an association between IMCL and insulin resistance might be modulated by oxidative capacity in skeletal muscle. We examined the hypothesis that 12 wk of exercise training would increase both IMCL and the oxidative capacity of skeletal muscle in older (67.

Ex vivo gene transfer to mature skeletal muscle by using adenovirus helper cells.

Background: Adenoviral gene transfer to adult skeletal muscle is hindered by several major limitations, including host immune responses and maturation-dependent loss of myofiber infectivity. Ex vivo gene delivery is more efficient than direct viral injection in surmounting maturation-dependent adenoviral transduction. Here we investigated the use of helper cells to improve the efficiency of ex vivo gene transfer to adult mouse skeletal muscle.

Improved sphincter contractility after allogenic muscle-derived progenitor cell injection into the denervated rat urethra.

Objectives: To study the physiologic outcome of allogenic transplant of muscle-derived progenitor cells (MDPCs) in the denervated female rat urethra.

Methods: MDPCs were isolated from muscle biopsies of normal 6-week-old Sprague-Dawley rats and purified using the preplate technique. Sciatic nerve-transected rats were used as a model of stress urinary incontinence.

Dystrophin delivery in dystrophin-deficient DMDmdx skeletal muscle by isogenic muscle-derived stem cell transplantation.

Duchenne's muscular dystrophy (DMD) is a lethal muscle disease caused by a lack of dystrophin expression at the sarcolemma of muscle fibers. We investigated retroviral vector delivery of dystrophin in dystrophin-deficient DMD(mdx) (hereafter referred to as mdx) mice via an ex vivo approach using mdx muscle-derived stem cells (MDSCs). We generated a retrovirus carrying a functional human mini-dystrophin (RetroDys3999) and used it to stably transduce mdx MDSCs obtained by the preplate technique (MD3999).

Muscle-derived stem cells seeded into acellular scaffolds develop calcium-dependent contractile activity that is modulated by nicotinic receptors.

Objectives: To explore the contractile activity and physiologic properties of muscle-derived stem cells (MDSCs) incorporated into small intestinal submucosa (SIS) scaffolds.

Methods: MDSCs were harvested from mice hind leg muscles using the preplate technique and stably transfected with a plasmid to express the LacZ reporter gene. Fifty different preparations of SIS cultured with MDSCs (MDSC/SIS) or SIS alone were incubated at 37 degrees C for 1, 4, and 8 weeks and also were mounted in a bath to measure the isometric contractions.

Muscle derived cell mediated ex vivo gene transfer to the lower urinary tract: comparison of viral vectors.

Gene therapy is a novel form of molecular medicine that may have a major impact on the future of human health care. We explored the efficacy of skeletal muscle derived cells (MDC) transduced with four viruses for ex vivo gene transfer into the lower urinary tract. Primary MDC were isolated from normal neonatal rats and transduced with: (1).

Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration.

Three populations of myogenic cells were isolated from normal mouse skeletal muscle based on their adhesion characteristics and proliferation behaviors. Although two of these populations displayed satellite cell characteristics, a third population of long-time proliferating cells expressing hematopoietic stem cell markers was also identified. This third population comprises cells that retain their phenotype for more than 30 passages with normal karyotype and can differentiate into muscle, neural, and endothelial lineages both in vitro and in vivo.