Effectiveness and Safety of Autologous Adipose-Derived Regenerative Cells for the Treatment of Urethral Strictures
Effectiveness and Safety of Autologous Adipose-Derived Regenerative Cells for the Treatment of Urethral Strictures
Autologous adipose-derived regenerative cells (ADRC) extracted using Celution 800/CRS System
 (Cytori Therapeutics Inc)from a portion of the fat harvested from the patient's front
 abdominal wall. ADRC will be administered one-time endoscopically into submucosal layer of
 urethra under eye control into the stricture site after mechanical dilation. This is a single
 arm study with no control. All patients receive cell therapy.
Fat tissue obtainment. Subjects will undergo liposuction under local anesthesia. In this
 procedure, Ringer's solution with the anesthetic lidocaine and vasoconstrictor adrenaline
 infused into the adipose compartment to minimize blood loss and contamination of the tissue
 by peripheral blood cells. 15 minutes later a hollow blunt-tipped 3 mm cannula introduced
 into the subcutaneous space through small (0.5 cm) incision. The cannula attached to syringe
 and under gentle suction moved through the adipose compartment, mechanically disrupting the
 fat tissue. Aspirate volume - approximately 150-200 cc. Procedure time - 30 minutes.

 ADRC isolation. Aspirated fat tissue placed into sterile vessel which inserted into Celution
 800/CRS System (Cytori Therapeutics Inc) - closed system for automated and standardized
 extraction and concentration of ADRC. Celution 800/CRS System drains excess of fluid from fat
 tissue and estimate it's volume After that lipoaspirate washed extensively with equal volumes
 of Ringer's solution to remove blood. At the end of this process System indicates required
 volume of enzyme reagent (Celase®) which should be added immediately by operator. After
 enzyme treatment Celution 800/CRS System automatically transfers isolated ADRC into washing
 compartment where ADRC washed and concentrated in 5 mL suspension. Tissue processing time -
 approximately 60 minutes. ADRC suspension match all requirements listed in technical
 documentation for Celution 800/CRS System. Obtained ADRC divided into 2 portions. First
 portion (0.2-0.5 mL) used for counting, viability and sterility assessment. Second portion
 placed into sterile syringe for injection.

 Urethral stricture dilation. Under direct vision HiWire® hydrophilic nitinol wire positioned
 through the urethra and exchanged for a stiff-bodied wire. After that S-Curve urethral
 dilators (Cook Medical Inc.) passed over the wire guide progressing from the smallest to the
 largest 24(Fr) appropriate size while maintaining the wire guide's position.

 Periurethral injection of ADRC. After dilation needle for injection introduced into urethra
 using endoscope. Urethra punctured several times circle-wise at the region of stricture at
 depth of 5 mm under endoscopic vision and 0.3-0.5 mL of ADRC suspension injected submucosally
 each time. Total volume of solution injected depends on stricture length and technical
 possibilities. Minimal injected volume - 3 mL, maximal - 4.5 ml. After fat micrograft
 injected, urethral balloon catheter placed and removed the following day.
Inclusion Criteria:

 -  Patient suffers from urethral strictures at least for 1 year

 -  Moderate and severe grade of obstructive voiding symptoms according to assessment made
 by investigator

 -  Patient is familiar with Participant information sheet.

 -  Patient signed informed consent form

 Exclusion Criteria:

 -Contraindications for local anesthesia

 For the patients undergone surgical treatment of prostate cancer:

 -  Cancer relapse

 -  prostate-specific antigen (PSA) level >0.008 ng/mL