Adipose-Derived Regenerative Cell Injection Therapy for Postprostatectomy Incontinence: A Phase I Clinical Study

Abstract

PurposeWe report our initial experience with transurethral injection of autologous adipose-derived regenerative cells (ADRCs) for the treatment of urinary incontinence after radical prostatectomy.Materials and MethodsAfter providing written informed consent, six men with persistent urinary incontinence after radical prostatectomy were enrolled in the study. Under general anesthesia, about 50 mL of adipose tissue was obtained from the patients by liposuction. ADRCs were obtained by separation with centrifugation using the Celution cell-processing device. A mixture of ADRCs and adipose tissue were transurethrally injected into the submucosal space of the membranous urethra. Functional and anatomical improvement was assessed using a 24-h pad test, validated patient questionnaire, urethral pressure profile, and magnetic resonance imaging (MRI) during 12-week follow-up.ResultsUrine leakage volume was improved with time in all patients in the 24-h pad test, with the exemption of temporal deterioration at the first 2 weeks post-injection in 2 patients. Subjective symptoms and quality of life assessed on the basis of questionnaire results showed similar improvement. The mean maximum urethral closing pressure increased from 44.0 to 63.5 cm H2O at 12 weeks after injection. MRI showed an increase in functional urethral length (from 6.1 to 8.3 mm) between the lower rim of the pubic bone and the bladder neck. Adverse events, such as pelvic pain, inflammation, or de novo urgency, were not observed in any case during follow-up.ConclusionThis study demonstrated that transurethral injection of autologous ADRCs can be a safe and effective treatment modality for postprostatectomy incontinence.

Treatment of male stress urinary incontinence using autologous adipose‐derived regenerative cells: Long‐term efficacy and safety

“…Magnetic resonance imaging showed a sustained presence of the injected adipose tissue, and enhanced ultrasonography showed a progressive increase in blood flow to the injected area in all patients. Thereafter, a Korean group treated six male SUI patients after RP following our procedure, and confirmed the improvement of subjective symptoms and quality of life, along with improved urethral sphincter function during a 12‐week follow‐up period …”

Stem cells and lower urinary tract dysfunction: Has its potential finally reached clinical maturity? ICI‐RS2018

“…No significant peri‐ or postoperative adverse events were reported. Similar results were reported in a study of six post‐RP incontinent patients who were injected a mixture of ADSCs and adipose tissue into the rhabdosphincter and submucosal space . In a rat model replicating post‐RP SUI and erectile dysfunction (ED), Yiou et al delivered human multipotent ADSCs (hMADSCs) directly into the electrocautery‐damaged sphincter and penis.…”

“…Thus, an ideal therapeutic modality for SUI would include revascularization, reinnervation, and striated muscle replenishment of the sphincter. Several preclinical studies have demonstrated various types of MSCs, injected periurethrally, to be efficacious . Most of these studies used rats or mice as animal models, and different techniques have been applied to cause SUI.…”

Precise injection of human mesenchymal stromal cells in the urethral sphincter complex of Göttingen minipigs without unspecific bulking effects

“…Swelling of the urethra immediately after application of aliquots summing up at a total volume of 1 mL did not change the urethral pressure profiles compared to the profiles acquired immediately prior to treatment. Moreover, to cause a bulking effect by cell injections, 20 mL of a suspension of autologous adipose‐derived cells were injected in the submucosal tissue of men . This is a considerably larger injection volume compared to the volumes applied in our study.…”

“…Deposition of hydrogels or other components in the submucosa and close to the urothelium layer of the sphincter complex may cause local swelling or bulking effects as observed by our injection test employing cadaveric sphincter samples. This of course is beneficial when bulking is needed to treat SUI . In contrast, in case of a regenerative cell therapy, injections of smaller volumes in deeper zones may be beneficial, because regeneration of the contractile sphincter apparatus will be facilitated when the regenerative cells are deposited close by.…”