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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 144935
Funding scheme Ambizione
Research institution
Institution of higher education University of Zurich - ZH
Main discipline Biomedical Engineering
Start/End 01.10.2012 - 30.09.2014
Approved amount 227'229.00
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Keywords (2)

Stem cells, muscles, Tissue engineering; GMP, clinical trial

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. We have currently adapted the methods used to handle animal muscle cells to human tissues and investigated the optimal method for cell injection in humans using magnet resonance imaging (MRI) and ultrasound (US). Currently we focus on  designing the first human trials in Switzerland.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
[Focal therapy-a new era in the treatment of prostate cancer].
Eberli Daniel, Mortezavi Ashkan, Sulser Tullio (2014), [Focal therapy-a new era in the treatment of prostate cancer]., in Praxis, 103(7), 391-7.
A novel animal model for external anal sphincter insufficiency.
Brügger Lukas, Inglin Roman, Candinas Daniel, Sulser Tullio, Eberli Daniel (2014), A novel animal model for external anal sphincter insufficiency., in International journal of colorectal disease, 29(11), 1385-92.
Ablative efficiency of 532-nm laser vaporization compared to transurethral resection of the prostate: results from a prospective three-dimensional ultrasound volumetry study.
Hermanns Thomas, Gross Oliver, Kranzbühler Benedikt, Hefermehl Lukas J, Poyet Cédric, Müller Alexander, Yap Stanley A, Michel Maurice S, Eberli Daniel, Müntener Michael, Zimmermann Matthias, Sulser Tullio, Seifert Hans-Helge (2014), Ablative efficiency of 532-nm laser vaporization compared to transurethral resection of the prostate: results from a prospective three-dimensional ultrasound volumetry study., in World journal of urology, 32(5), 1267-74.
Adipose-derived stem cells (ADSCs) and muscle precursor cells (MPCs) for the treatment of bladder voiding dysfunction.
Tremp Mathias, Salemi Souzan, Largo Remo, Andersson Karl-Erik, A Plock Jan, Aboushwareb Tamer, Sulser Tullio, Eberli Daniel (2014), Adipose-derived stem cells (ADSCs) and muscle precursor cells (MPCs) for the treatment of bladder voiding dysfunction., in World journal of urology, 32(5), 1241-8.
Erratum to: Adipose-derived stem cells (ADSCs) and muscle precursor cells (MPCs) for the treatment of bladder voiding dysfunction.
Tremp Mathias, Salemi Souzan, Largo Remo, Andersson Karl-Erik, Plock Jan, Aboushwareb Tamer, Sulser Tullio, Eberli Daniel (2014), Erratum to: Adipose-derived stem cells (ADSCs) and muscle precursor cells (MPCs) for the treatment of bladder voiding dysfunction., in World journal of urology, 32(5), 1249-1249.
Health technology assessment in evolution - focal therapy in localised prostate cancer.
Valerio Massimo, Emberton Mark, Barret Eric, Eberli Daniel, Eggener Scott E, Ehdaie Behfar, Jichlinski Patrice, Ward John F, Ahmed Hashim U (2014), Health technology assessment in evolution - focal therapy in localised prostate cancer., in Expert review of anticancer therapy, 1-9.
Lateral temperature spread of monopolar, bipolar and ultrasonic instruments for robot-assisted laparoscopic surgery.
Hefermehl Lukas J, Largo Remo A, Hermanns Thomas, Poyet Cédric, Sulser Tullio, Eberli Daniel (2014), Lateral temperature spread of monopolar, bipolar and ultrasonic instruments for robot-assisted laparoscopic surgery., in BJU international, 114(2), 245-52.
A bilayered hybrid microfibrous PLGA-Acellular matrix scaffold for hollow organ tissue engineering
Horst Maya, Madduri Srinivas, Milleret Vincent, Sulser Tullio, Gobet Rita M., Eberli Daniel (2013), A bilayered hybrid microfibrous PLGA-Acellular matrix scaffold for hollow organ tissue engineering, in Biomaterials, 34(5), 1537-1545.
Botulinum toxin A and B raise blood flow and increase survival of critically ischemic skin flaps.
Schweizer Dennis F, Schweizer Riccardo, Zhang Shengye, Kamat Pranitha, Contaldo Claudio, Rieben Robert, Eberli Daniel, Giovanoli Pietro, Erni Dominique, Plock Jan A (2013), Botulinum toxin A and B raise blood flow and increase survival of critically ischemic skin flaps., in The Journal of surgical research, 184(2), 1205-13.
Computed tomography perfusion imaging of renal cell carcinoma: systematic comparison with histopathological angiogenic and prognostic markers.
Reiner Caecilia S, Roessle Matthias, Thiesler Thore, Eberli Daniel, Klotz Ernst, Frauenfelder Thomas, Sulser Tullio, Moch Holger, Alkadhi Hatem (2013), Computed tomography perfusion imaging of renal cell carcinoma: systematic comparison with histopathological angiogenic and prognostic markers., in Investigative radiology, 48(4), 183-91.
Continuous low-dose aspirin therapy in robotic-assisted laparoscopic radical prostatectomy does not increase risk of surgical hemorrhage
Mortezavi Ashkan, Hermanns Thomas, Hefermehl Lukas J., Spahn Donat Rudolf, Seifert Burkhardt, Weber Damian, Brunnschweiler Simone, Schmid Daniel Max, Sulser Tullio, Eberli Daniel (2013), Continuous low-dose aspirin therapy in robotic-assisted laparoscopic radical prostatectomy does not increase risk of surgical hemorrhage, in Journal of Laparoendoscopic and Advanced Surgical Techniques, 23(6), 500-505.
Controlled oxygen release from pyridone endoperoxides promotes cell survival under anoxic conditions.
Benz Sebastian, Nötzli Sarah, Siegel Jay S, Eberli Daniel, Jessen Henning J (2013), Controlled oxygen release from pyridone endoperoxides promotes cell survival under anoxic conditions., in Journal of medicinal chemistry, 56(24), 10171-82.
Engineering functional bladder tissues
Horst Maya, Madduri Srinivas, Gobet Rita M., Sulser Tullio, Milleret Vinzent, Hall Heike Kenton, Atala Anthony, Eberli Daniel (2013), Engineering functional bladder tissues, in Journal of Tissue Engineering and Regenerative Medicine, 7(7), 515-522.
Hemostatic properties and the role of cell receptor recognition in human hair keratin protein hydrogels
Burnett Luke R., Rahmany Mária B., Richter Jillian R., Aboushwareb Tamer A., Eberli Daniel, Ward Catherine L., Orlando Giuseppe, Hantgan Roy R., Van Dyke Mark E. (2013), Hemostatic properties and the role of cell receptor recognition in human hair keratin protein hydrogels, in Biomaterials, 34(11), 2632-2640.
Increased porosity of electrospun hybrid scaffolds improved bladder tissue regeneration
Maya Horst, Vincent Milleret, Nötzli Sarah, Madduri Srinivas, Tullio Sulser, Rita Gobet, Eberli Daniel (2013), Increased porosity of electrospun hybrid scaffolds improved bladder tissue regeneration, in Journal of Biomedical Materials Research - Part A, 00A.
Influence of micro and submicro poly(lactic-glycolic acid) fibers on sensory neural cell locomotion and neurite growth.
Binder Carmen, Milleret Vincent, Hall Heike, Eberli Daniel, Lühmann Tessa (2013), Influence of micro and submicro poly(lactic-glycolic acid) fibers on sensory neural cell locomotion and neurite growth., in Journal of biomedical materials research. Part B, Applied biomaterials, 101(7), 1200-8.
Iterative reconstructions versus filtered back-projection for urinary stone detection in low-dose CT.
Winklehner Anna, Blume Iris, Winklhofer Sebastian, Eberli Daniel, Gnannt Ralph, Frauenfelder Thomas, Alkadhi Hatem (2013), Iterative reconstructions versus filtered back-projection for urinary stone detection in low-dose CT., in Academic radiology, 20(11), 1429-35.
Multisystem neuroprosthetic training improves bladder function after severe spinal cord injury
Horst Maya, Heutschi Janine, Van Den Brand Rubia J., Andersson Karl Erik, Gobet Rita M., Sulser Tullio, Courtine Grégoire, Eberli Daniel (2013), Multisystem neuroprosthetic training improves bladder function after severe spinal cord injury, in Journal of Urology, 189(2), 747-753.
Myoblasts inhibit prostate cancer growth by paracrine secretion of tumor necrosis factor-α
Stölting, Ferrari Stefano, Handschin Christoph, Becskei Attila, Provenzano Maurizio, Sulser Tullio, Eberli Daniel (2013), Myoblasts inhibit prostate cancer growth by paracrine secretion of tumor necrosis factor-α, in Journal of Urology, 189(5), 1952-1959.
Skeletal Muscle Regeneration for Clinical Application
Azzabi Fahd (2013), Skeletal Muscle Regeneration for Clinical Application, in Andrades Jose A (ed.), INTECH, Rijeka, Ch27.
Split-bolus dual-energy CT urography: protocol optimization and diagnostic performance for the detection of urinary stones
Karlo CA Gnannt R Winklehner A Fischer MA Donati OF Eberli D Sulser T Alkadhi H Stolzmann P. (2013), Split-bolus dual-energy CT urography: protocol optimization and diagnostic performance for the detection of urinary stones, in Abdomianl Imaging, 1136.
Automated tube potential selection for standard chest and abdominal CT in follow-up patients with testicular cancer: Comparison with fixed tube potential
Gnannt Ralph, Winklehner Anna, Eberli Daniel, Knuth Alexander K., Frauenfelder Thomas, Alkadhi Hatem (2012), Automated tube potential selection for standard chest and abdominal CT in follow-up patients with testicular cancer: Comparison with fixed tube potential, in European Radiology, 22(9), 1937-1945.
Bryophyllum pinnatum inhibits detrusor contractility in porcine bladder strips--a pharmacological study towards a new treatment option of overactive bladder.
Schuler V, Suter K, Fürer K, Eberli D, Horst M, Betschart C, Brenneisen R, Hamburger M, Mennet M, Schnelle M, Simões-Wüst A P, von Mandach U (2012), Bryophyllum pinnatum inhibits detrusor contractility in porcine bladder strips--a pharmacological study towards a new treatment option of overactive bladder., in Phytomedicine : international journal of phytotherapy and phytopharmacology, 19(10), 947-51.
Influence of the fiber diameter and surface roughness of electrospun vascular grafts on blood activation
Milleret Vincent, Hefti Thomas, Hall Heike, Vogel Viola, Eberli Daniel (2012), Influence of the fiber diameter and surface roughness of electrospun vascular grafts on blood activation, in ACTA BIOMATERIALIA, 8(12), 4349-4356.
Intrafascial dissection significantly increases positive surgical margin and biochemical recurrence rates after robotic-assisted radical prostatectomy
Mortezavi, Hermanns Thomas, Seifert Hans Helge, Wild Peter J., Schmid Daniel Max, Sulser Tullio, Eberli Daniel (2012), Intrafascial dissection significantly increases positive surgical margin and biochemical recurrence rates after robotic-assisted radical prostatectomy, in Urologia Internationalis, 89(1), 17-24.
Muscle Precursor Cells for the Restoration of Irreversibly Damaged Sphincter Function
Eberli Daniel, Aboushwareb Tamer, Soker Shay, Yoo James J., Atala Anthony (2012), Muscle Precursor Cells for the Restoration of Irreversibly Damaged Sphincter Function, in CELL TRANSPLANTATION, 21(9), 2089-2098.
Paracrine effects of mesenchymal stem cells enhance vascular regeneration in ischemic murine skin
Schlosser Stefan, Dennler Cyrill, Schweizer Riccardo, Eberli Daniel, Stein Jens V., Enzmann Volker, Giovanoli Pietro, Erni Dominique, Plock Jan Alexander (2012), Paracrine effects of mesenchymal stem cells enhance vascular regeneration in ischemic murine skin, in Microvascular Research, 83(3), 267-275.
Bone marrow-derived mesenchymal stromal cells improve vascular regeneration and reduce leukocyte-endothelium activation in critical ischemic murine skin in a dose-dependent manner.
Schweizer Riccardo, Kamat Pranitha, Schweizer Dennis, Dennler Cyrill, Zhang Shengye, Schnider Jonas T, Salemi Souzan, Giovanoli Pietro, Eberli Daniel, Enzmann Volker, Erni Dominique, Plock Jan A, Bone marrow-derived mesenchymal stromal cells improve vascular regeneration and reduce leukocyte-endothelium activation in critical ischemic murine skin in a dose-dependent manner., in Cytotherapy.
The Combination of Electric Current and Copper Promotes Neuronal Differentiation of Adipose-Derived Stem Cells.
Jaatinen L, Salemi S, Miettinen S, Hyttinen J, Eberli D, The Combination of Electric Current and Copper Promotes Neuronal Differentiation of Adipose-Derived Stem Cells., in Annals of biomedical engineering.
The role of donor age and gender in the success of human muscle precursor cell transplantation.
Stölting Meline N L, Hefermehl Lukas J, Tremp Mathias, Azzabi Fahd, Sulser Tullio, Eberli Daniel, The role of donor age and gender in the success of human muscle precursor cell transplantation., in Journal of tissue engineering and regenerative medicine.
Viability, Differentiation Capacity, and Detectability of Super-Paramagnetic Iron Oxide-Labeled Muscle Precursor Cells for Magnetic-Resonance Imaging.
Azzabi Fahd, Rottmar Markus, Jovaisaite Virginija, Rudin Markus, Sulser Tullio, Boss Andreas, Eberli Daniel, Viability, Differentiation Capacity, and Detectability of Super-Paramagnetic Iron Oxide-Labeled Muscle Precursor Cells for Magnetic-Resonance Imaging., in Tissue engineering. Part C, Methods.

Collaboration

Group / person Country
Types of collaboration
Institute of Regenerative Medicine, Wake Forest University United States of America (North America)
- Publication
Clinical Trial Center, University Hospital, Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Exchange of personnel
Pathology, University Hospital, Zürich Switzerland (Europe)
- Publication
Institute of Anatomy, University Hospital, Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Department of Radiology, University Hospital, Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Stem Cell Research Unit Graz Austria (Europe)
- Industry/business/other use-inspired collaboration
University Hospital Zürich Switzerland (Europe)
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
TERMIS-AM 2014 Individual talk Monitoring Of In Vivo Fiber Formation Of Muscle Precursor Cells Via Magnetization Transfer (MT)-MRI 15.10.2014 Washington D.C., United States of America Eberli Daniel;
TERMIS-AM 2014 Individual talk Differentiated Adipose Derived Stem Cells for Functional Smooth Muscle Bioengineering 15.10.2014 Washington D.C., United States of America Eberli Daniel;
TERMIS-AM 2014 Poster Role of Autophagy in the Differentiation of Adipose Derived Stem Cells to Functional Smooth Muscle Cells for Urologic Tissue Engineering 15.10.2014 Washington D.C., United States of America Eberli Daniel;
TERMIS-AM 2014 Individual talk In Vivo Evaluation Of Oxygen Releasing Suture Material For Improved Wound Healing In Hypoxic Environments 15.10.2014 Washington D.C., United States of America Eberli Daniel;
TERMIS-AM 2014 Poster Non-Invasive Tracking of Muscle Precursor Cells for Sphincter Muscle Engineering 15.10.2014 Washington D.C., United States of America Eberli Daniel;
TERMIS-AM 2014 Individual talk Neuronal differentiation of adipose-derived stem cells by electric current and copper for bladder engineering 14.10.2014 Washington D.C., United States of America Eberli Daniel;
70. Jahresversammlung, SGU 2014 Poster A retrospective analysis of urinary tract infections, resistance patterns and effectiveness of antimicrobial perioperative prophylaxis for transurethral procedures. 05.09.2014 Montreux, Switzerland Eberli Daniel;
70. Jahresversammlung, SGU 2014 Poster „Fokale Therapie des Prostatakarzinoms: Ist die Zeit reif?“ 04.09.2014 Montreux, Switzerland Eberli Daniel;
70. Jahresversammlung, SGU 2014 Poster Template Mapping Biopsy (TMB) of the Prostate 04.09.2014 Montreux, Switzerland Eberli Daniel;
70. Jahresversammlung, SGU 2014 Poster Extraction strings for ureteric stents: is there an increased risk for urinary tract infections? 04.09.2014 Montreux, Switzerland Eberli Daniel;
70. Jahresversammlung, SGU 2014 Poster Needle biopsy performed in a tertiary care center results in significantly less clinically relevant undergrading of prostate cancer 04.09.2014 Montreux, Switzerland Eberli Daniel;
70. Jahresversammlung, SGU 2014 Poster Reduced autophagy levels are associated with a higher Gleason score, tumor stage and an increased rate of prostate cancer specific death 03.09.2014 Montreux, Switzerland Eberli Daniel;
70. Jahresversammlung, SGU 2014 Poster The Role of Autophagy in the Differentiation of Adipose Derived Stem Cells to Functional Smooth Muscle Cells for Urologic Tissue Engineering 03.09.2014 Montreux, Switzerland Eberli Daniel;
70. Jahresversammlung, SGU 2014 Poster Non-invasive tracking of muscle precursor cells for sphincter muscle engineering 03.09.2014 Montreux, Switzerland Eberli Daniel;
70. Jahresversammlung, SGU 2014 Poster Monitoring Of In Vivo Fiber Formation Of Muscle Precursor Cells Via Magnetization Transfer (MT)-MRI 03.09.2014 Montreux, Switzerland Eberli Daniel;
AUA American Urological Association 2014 Poster Non-Invasive Tracking of Muscle Precursor Cells for Sphingter Muscle Engineering 17.05.2014 Orlando, United States of America Eberli Daniel;
AUA American Urological Association 2014 Individual talk Controlled Oxygen Release from Pyridone Endoperoxides for Urologic Tissue Engineering Applications 17.05.2014 Orlando, United States of America Eberli Daniel;
EAU European Urological Association 2014 Individual talk Stem cells and scaffolds: The future 14.04.2014 Stockholm, Sweden Eberli Daniel;
69.Jahresversammlung,SGU Individual talk The role of donor age and gender on the success of autologous human muscle precursor cell transplantation for sphincter insufficiency 11.09.2013 Genf, Switzerland Eberli Daniel;
69.Jahresversammlung,SGU Individual talk The Role of Autophagy in the differentiation of adipose derived stem cells to functional smooth muscle bioengineering 11.09.2013 Genf, Switzerland Eberli Daniel;
EAU European Urological Association Individual talk Summary on stem cell therapy in the near future 20.08.2013 milano, Italy Eberli Daniel;
EAU European Urological Association Individual talk Regenerative urology for children and adults 14.08.2013 milano, Italy Eberli Daniel;
AUA American Urology Association Poster Bioengineered skeletal muscle for the treatment of sphincter insufficiency characterized by MRI relaxometry 08.05.2013 San Diego, United States of America Azzabi Zouraq Fahd; Eberli Daniel;
AUA American Urology Association Poster Defining the diffusion restricition in MRI caused by prostate cancer cells:a quantitative in-vitro study 08.05.2013 San Diego, United States of America Eberli Daniel; Azzabi Zouraq Fahd;
AUA American Urology Association Poster Scaffold with neurotrophic and topographic factors for improved autonomic innervation for bladder engineering 06.05.2013 San Diego, United States of America Eberli Daniel;
AUA American Urology Association Poster Continous low-dose aspirin therapy in robotic-assisted laparoscopic radical prostatetectomy does not increase risk of surgical haemorrhage 06.05.2013 San Diego, United States of America Eberli Daniel;
AUA American Urology Association Poster Long-term oncological outcome following laparoscopic radical prostatectomy for clinically localized prostate cancer 06.05.2013 San Diego, United States of America Eberli Daniel;
AUA American Urology Association Poster Oxygen releasing sutrute material improves wound healing in bowel anastomosis 06.05.2013 San Diego, United States of America Eberli Daniel;
TERMIS Worldcongress 2012 Poster Muscle precursor cells for the treatment of fecal incontinence 01.10.2012 wien, Austria Eberli Daniel;
TERMIS Worldcongress 2012 Poster Age and Gender limitation for the bioengineering of contractile muscle tissue for human muscle precursor cells 01.10.2012 wien, Austria Eberli Daniel;
TERMIS Worldcongress 2012 Poster CULTURING HUMAN MUSCLE PRECURSOR CELLS (MPCS) WITH XENO-FREE MEDIUM: GMP AND CLINICAL APPLICATION PREPARATION 01.10.2012 wien, Austria Azzabi Zouraq Fahd;
TERMIS Worldcongress 2012 Poster Adipose-derived stem cells and muscle precursor cells for the treatment of bladder voiding dysfunction 01.10.2012 Wien, Austria Eberli Daniel;
TERMIS Worldcongress 2012 Poster Muscle regeneration and tracking of human Muscle Precursor Cells by MRI in vivo 01.10.2012 wien, Austria Azzabi Zouraq Fahd;
TERMIS Worldcongress 2012 Poster In vivo electromagnetic stimulation supports muscle regeneration after stem cell injection by boosting muscular metabolism and stimulating nerve ingrowth 01.10.2012 Wien, Austria Eberli Daniel;
Oral Biology Colloquium Individual talk Soft Tissue Engineering; Promising Cells and Biomaterials 01.10.2012 Center of Dental Medicine, Zurich, Switzerland Eberli Daniel;
TERMIS Worldcongress 2012 Poster the effect of porosity on tissue ingrowth and vascularization in electrospun hybrid scaffolds for bladder regeneration 01.10.2012 Wien, Austria Eberli Daniel;
TERMIS Worldcongress Individual talk Pre-Establishment of a Vascular Network for Urinary Sphincter Engineering 01.10.2012 Wien, Austria Eberli Daniel;
Austrian Cluster for Tissue Regeneration Individual talk Functional Soft Tissue Engineering 01.10.2012 Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austria Eberli Daniel;


Self-organised

Title Date Place
BIO 435 Vorlesung Humanbiologie UZH 18.02.2013 Zürich, Switzerland

Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Behandlung der Blasenschwäche: Was bringt uns die Zukunft 24.10.2012 Zürich, Switzerland Eberli Daniel;


Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Der Inkontinenz den Riegel schieben Horizonte German-speaking Switzerland Western Switzerland Rhaeto-Romanic Switzerland Italian-speaking Switzerland 2013
Print (books, brochures, leaflets) Vom Labor ans Krankenbett/ Puls USZ German-speaking Switzerland 2013

Awards

Title Year
SIWF-Award fur besonderes Engagement in der ärztlichen Weiterbildung (FMH) Teaching Award of the Swiss Medical Association (FMH) 2014
1st Basic Research Prize of the Swiss Urological Association Increased Porosity of electrospun hybrid Scaffolds improve Bladder Tissue Regeneration Horst M, Millert V, Nötzli S, Madduri S, Sulser T, Gobet R, Eberli D Annual Meeting of the Swiss Urological Association, Genva 2013 2013
Research Grant Innovations-Fond University Zürich for the clinical research project “Focal Therapy for Prostate Cancer”. 2013
C.E. Alken Research Prize (KelmHjälmas First Prize Basic Science) Collagen/Silk Fibroin based hybrid Biomaterial with sustained release of Nerve Growth Factor for axonal Regeneration in Bladder Tissue Engineering Madduri S, Gobet R , Sulser T , Eberli D 23nd Annual Meeting oft the European Society for Pediatric Urology, Zurich, 2012 2012
C.E. Alken-Preis für hervorragende Wissenschaftliche Leistungen auf dem Gebiet der Urologie. “Hybrid-Biomaterial mit definierten Oberflächenmerkmalen und Wachstumsfaktoren unterstützt die Nervenregeneration beim Blasen züchten” C.E. Alken-Preisträgertreffen 2012, München. 2012
Felix Largiadèr-Preis Stem Cells for the Treatment of Anal Incontinence. Brügger L, Inglin R. Candinas D. Sulser T. Eberli D of the Swiss Surgical Society, Annual meeting 2012 2012
Posterprize Stem Cell Research, Annual Meeting AUA Stöling M, Handshin Ch, Becskei A, Tullio S, Eberli D In vivo Electromagnetic stimulation supports muscle regeneration after stem cell injection by boosting muscular metabolism and stimulating nerve ingrowth Annual Meeting of the American Urological Assocciation, Atlanta 2012
Research prize: Best Poster of Session Stölting M.N.L, Kramer S, Ametamey S, Ferrari S, Becskei A, Sulser T, Eberli D. Muscle Precursor Cells are safe for the treatment of urinary incontinence after surgery for prostate cancer Annual Meeting of the European Assocciation of Urology, Vienna 2011. 2012

Patents

Title Date Number Inventor Owner
Prevention of bacterial adherence and growth in an urological implant 01.01.2013 PCT/EP2011/061389

Associated projects

Number Title Start Funding scheme
126230 Muscle Precursor Cells for the treatment of Urinary Incontinence 01.10.2009 Ambizione
136197 Improving human muscle engineering by PGC-1alpha expression and molecular imaging using positron emission tomography (PET) 01.01.2012 Sinergia

Abstract

Grant Prolongation, Please see also „Cover letter and Applicaiton“ 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 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 are limited by complications.Recently, we were able to publish our results on 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. Over the last 2.5 years we have followed the time line outlined in the SCORE proposal and have gained substantial research data supporting an clincial trial. 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), will be certified soon.We have proposed a research plan with the ultimate goal of conducting a phase I clinical trial within four years. We envision initiating clinical trials in 2013, starting with sphincter reconstruction, using a cell-based strategy. The approach presented here was chosen due to the simple and minimal 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 micturation 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 muscles cells 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 minimal invasive techniques for muscle cell injectiona-Determine the feasibility of minimal 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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