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Muscle Precursor Cells for the treatment of Urinary Incontinence

English title Muscle Precursor Cells for the treatment of Urinary Incontinence
Applicant Eberli Daniel
Number 126230
Funding scheme Ambizione
Research institution Urologische Klinik und Poliklinik Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Biomedical Engineering
Start/End 01.10.2009 - 30.09.2012
Approved amount 682'321.00
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All Disciplines (2)

Discipline
Biomedical Engineering
Surgery

Keywords (7)

Tissue engineering; Urinary incontinence; Muscle precursor cell; Clinical trial; Regenerative medicine; cell therapy; incontinence

Lay Summary (English)

Lead
Lay summary
Urinary incontinence, the involuntary loss of urine, still remains a mayor medical issue with approximately 20% of women affected. The quality of life of patients with urinary incontinence is severely affected. The main cause for urinary incontinence is damage of the sphincter muscle, which occurs during childbirth, surgical treatments or as an effect of aging. Current surgical treatment options enable recovery of continence with various outcomes. However, definitive correction of underlying etiology, the damages muscle, has not been accomplished. Furthermore, these options only offer short-term relief and the overall success of these therapies are limited by complications.Recently, we were able to demonstrate the effectiveness of using muscle cells in the treatment of sphincter insufficiency in a large animal model. A small biopsy of a leg muscle was taken and the cells expanded in the laboratory. These cells were then injected into the damages sphincter muscle. Our results showed that injected muscle cells were able to form new sphincter muscle and achieve 80% of sphincter function after 6 months.The approach used was chosen due to the simple procedure needed for the functional restoration of the urinary sphincter. The rationale for implanting muscle into the damaged sphincter muscle is two-fold. First, the generation of a muscle tissue mass will achieve a volume effect that would increase the sphincter pressure, thus controlling incontinence. Second, implantation of muscle cells will achieve restoration of sphincter function through the formation of new nerves, which control continence over time. If successful this would clearly demonstrate a major medical breakthrough. Our research is structured into different steps. First, we will adapt the methods used to handle animal muscle cells to human tissues. Second, we will investigate the optimal method for cell injection in humans using magnet resonance imaging (MRI) and ultrasound (US). Third, we will design and conduct the first human trials in Switzerland.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
111111 Transforming Pius Branzeu Center of Laporoscopic Surgery and Microsurgery (PBCLSM) Timisoara into Eastern European Zonal Center of Development and Research in Laparascopic Surgery 01.01.2006 SCOPES
145007 Hyperpolarized Magnetic Resonance Metabolic Imaging - From Bench to Bedside 01.08.2013 R'EQUIP
144935 Muscle Precursor Cells for the treatment of Urinary Incontinence 01.10.2012 Ambizione
100272 Gewebe- und Organregeneration in der Urologie mit Hilfe von 'Tissue Engineering' 01.04.2003 Fellowships for prospective researchers
136197 Improving human muscle engineering by PGC-1alpha expression and molecular imaging using positron emission tomography (PET) 01.01.2012 Sinergia

Abstract

Urinary incontinence, the involuntary loss of urine, still remains a major medical issue with approximately 20% of women affected. The quality of life of patients with urinary incontinence is severely affected and the incurring healthcare costs are significant. The main cause for stress urinary incontinence (SUI) is damage of the sphincter muscle, which occurs during childbirth, surgical treatments or as an effect of aging. Current surgical treatment options enable recovery of continence with various outcomes. However, definitive correction of underlying etiology has not been accomplished. Furthermore, these options only offer short-term relief and the overall success of these therapies is limited by complications.Recently, we were able to demonstrate the effectiveness of using autologous muscle precursor cells (MPCs) in the treatment of sphincter insufficiency in a large animal model. Our results showed that injected muscle cells were able to form new sphincter muscle and achieve 80% of sphincter function after 6 months. Therefore, on the basis of 4 years of active animal research at Harvard and Wake Forest University the main goal of this proposal is to successfully translate this research into clinics. The legal and ethical environment in Switzerland offers an optimal platform for safe and rapid clinical evaluation. Furthermore, the University of Zurich and the Department of Urology have committed to the formation of a laboratory for urologic tissue engineering and a good manufacturing practice (GMP) laboratory, supported by Swiss national fund (SNF), is under construction. We propose a research plan with the ultimate goal of conducting a phase I clinical trial within four years. We envision initiating clinical trials after year three, starting with sphincter reconstruction, using a cell-based strategy. The approach presented here was chosen due to the simple and minimally invasive nature of the procedure for the functional restoration of the urinary sphincter. The rationale for implanting muscle into the sphincter region is two-fold. First, the generation of a muscle tissue mass within the bladder neck region will achieve a bulking effect that would increase the sphincter pressure, thus controlling incontinence. Second, implantation of muscle cells will achieve restoration of sphincter function through innervation, which control continence and micturition over time. Simultaneously to preparing the clinical trial, we will pursue further scientific investigations and preclinical studies necessary in the future to applying genetic regenerative approach to the restoration of the SUI.We hypothesize that autologous MPCs injected into damaged sphincter muscles of patients with urinary incontinence are able to form new functional muscle tissue, support sphincter function and significantly improve the quality of life in human, as it has been the case in our large animal model. We will test this hypothesis in the following specific aims and, in this application, we ask for support to complete these aims. Aim 1: Optimize human muscle cell procedures to restore the urinary sphinctera-Define a reliable human muscle cell culture system for human muscle cell therapyb-Analyze engineered human muscle for functional tissue restorationc-Determine the donor age and gender limitations for the use of autologous muscle cellsd-Determine if genetically modified muscle precursor cells improve sphincter muscle functionAim 2: Evaluation of imaging guided minimally invasive techniques for muscle cell injectiona-Determine the feasibility of minimally invasive techniques for MPC injection using different imaging modalitiesb-Construct a needle guidance that satisfies international requirements for medical devicesc-Evaluate the use of nanoparticles for in vivo cell trackingAim 3: Restore damaged sphincter muscle function using muscle cell therapy in patients: phase I/II Triala-Establish a reproducible procedure for cellular therapy of urinary incontinence in patients respecting GMP and good clinical practices (GCP) requirementsb-Analyze the regenerated sphincter muscle tissue using non-invasive imaging techniquesc-Evaluate the clinical impact of MPC therapy using standard clinical assessment
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