Multisystem Cell Therapy for Improvement of Urinary Continence

muscle precursor cells (MPCs) will be isolated from biopsies of the lower leg of patients, seeded, expanded and cultivated in vitro in a GMP facility to generate vital muscle cells dedicated for implantation.

These muscle cells exhibit myogenic phenotype (IHC and flow cytometry) and therefore morphological and histological prerequisites approximating the properties of native skeletal muscle tissue. The muscle progenitor cells shall be applied in external sphincter muscle for the treatment of patients with stress urinary incontinence.

Inclusion criteria

Adult women 20y-60y

• Incontinence >/= grade I since at least 6 months
• Predominant clinical diagnosis of SUI
• Candidate for a surgical treatment (artificial urinary sphincter, synthetic compressive tapes or adjustable balloons).
• Post void residual volume of <100 ml (exclusion of overflow incontinence)
• Can independently use toilet without difficulty
• Capacity to answer the questionnaires of evaluation
• Negative blood test for: Human immunodeficiency virus (HIV 1/2), Hepatitis B HBsAg, Anti HBc, Hepatitis C Anti-HCV-Ab, Syphilis
• Competent to comprehend, sign and date informed consent form before any study-specific procedure is performed

Exclusion criteria

• History of anti-incontinence or prolapse surgery.
• Previous diagnosis of any of the following conditions, disorders, or diseases of the urinary tract:

• Clinically significant cystocele or rectocele
• Ureteric bladder, urethral or rectal fistula
• Uncorrected congenital abnormality leading to urinary incontinence
• Interstitial cystitis
• Urinary urgency that results in leakage (as a predominant symptom)
• Adult enuresis
• Urodynamically proven detrusor instability
• Sensory urgency defined as first sensation of bladder fill (urge to void) of <100 ml; bladder capacity of <300 ml
• No sensation at any time during the simple filling cystometry procedure
• Known urethral stenosis (ureterocystoscopy) or urethral diverticulum
• History of urogenital cancer or history of pelvic radiotherapy
• Women who are pregnant, breast feeding or <12 months postpartum Note: Female subjects who are surgically sterilized, hysterectomized or post-menopausal for longer than 2 years are not considered as having child bearing potential. No pregnancy test will be performed for this population.
• Untreated symptomatic urinary tract infection
• Fever (as defined by ≥ 38,5°C, axillar measurement), any infectious disease, cold or flu within the last 7 days
• Unstable severe systemic disease including uncontrolled hypertension, unstable angina, or myocardial infarction, severe coagulation disorders, bleeding diathesis, emboli, thrombophlebitis, infectious diseases, poor wound healing, and poorly controlled diabetes mellitus within 6 months before enrolment
• Any organic or psychiatric disorder that, in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results.
• Known allergy or intolerance of at least one of the active ingredients or excipients of the investigational products
• Known allergy or intolerance of Penicillin or Streptomycin
• Known genetically determined or acquired muscular disease.
• Known Neurological disorder (Parkinson's disease, multiple sclerosis, spina bifida, medullary traumatism).
• Medication regimen including estrogens, anti-estrogens or diuretics where dose and/or frequency has not been stable for at least the past 12 weeks or is anticipated to change during the course of the study.
• Chronic use of any of the following drugs and not stopped for at least 2 weeks prior to inclusion into the study: selective serotonin and norepinephrine reuptake inhibitor antidepressant (SSNRI), alpha-receptor antagonists/agonists, beta-3-receptor agonists or anticholinergic/-muscarinic drugs.
• Chronic use of any of the following drugs and not stopped for at least 6 months prior to inclusion into the study: Antidepressants or neuroleptic drugs.