Feasibility of cell therapy against stress urinary incontinence (SUI) has been debated(1-3). Adipose derived stromal cells (ADSC) either differentiate into striated muscle, enhance the nerve growth after denervation, or increase tissue bulking through the synthesis of extracellular matrices. In the third mechanism, obstruction side effect was concerned. In this study, we exploited the rat model to investigate the mechanism how ADSC ameliorate SUI and estimate the potential risk of side effect.

Vaginal distension (VD) rats were generated to mimic stress urinary incontinence. ADSC was isolated from the subcutaneous fat and autografted around the urethral sphincter. With or without VD, each rat split into three groups (i.e. no-injection group, injection of ADSC alone or injection of ADSC plus extracellular scaffolds), were subject to leak point pressure (LPP) measurement. LPP was measured seven or fourteen days after injection of ADSC through placing a catheter inside the bladder. There was characteristic waveform of LPP and we counted the second peak as a ‘void pattern’.

VD significantly decreased the frequency of void pattern emergence and the level of LPP. In the absence of VD, injection ADSC hardly affected the level of LPP (no obstruction effect). In the presence of VD, however, injection of ADSC significantly increased the frequency of void pattern emergence and the level of LPP. Addition of the extracellular scaffolds displayed the negligible effects during time windows examined.

ADSC transplantation ameliorated the defective voiding caused by VD.

ADSC appeared to display ‘bulking effects’ contingent upon tissue damages (i.e. VD) exist. Context dependent activation of transplanted ADSC should be investigated thoroughly.

Yamamoto T, Gotoh M, Hattori R, Toriyama K, Kamei Y, Iwaguro H, et al. Periurethral injection of autologous adipose-derived stem cells for the treatment of stress urinary incontinence in patients undergoing radical prostatectomy: report of two initial cases. Int J Urol 2010;17:75-82.
Gotoh M, Yamamoto T, Kato M, Majima T, Toriyama K, Kamei Y, et al. Regenerative treatment of male stress urinary incontinence by periurethral injection of autologous adipose-derived regenerative cells: 1-year outcomes in 11 patients. Int J Urol 2014;21:294-300.
Shimizu S, Yamamoto T, Nakayama S, Hirakawa A, Kuwatsuka Y, Funahashi Y, et al. Design of a single-arm clinical trial of regenerative therapy by periurethral injection of adipose-derived regenerative cells for male stress urinary incontinence in Japan: the ADRESU study protocol. BMC Urol 2017;17:89.