Therapeutic effect of adipose-derived regenerative cells on bladder function in rats with underactive bladder.

We examined the effect of adipose-derived regenerative cells (ADRC) on bladder functions in a rat model of detrusor underactivity (DU) induced by bladder over-distention. Adult female Sprague Dawley rats were divided into 3 groups: sham group (control); over-distention group; and over-distention with ADRC treatment group. Bladder was over-distended with saline (2.7mL) on day 1, 8, 15 and 22 of the study. ADRCs, which were harvested from male F344 rats, expanded via culture, were injected into the bladder wall at day 15. Cystometry and in vitro organ bath functional studies were performed on day 28. Moreover, histological assessment of the bladder was performed. In cystometry, significant prolongation of the inter-contraction interval (ICI) and decrease of voiding efficiency (VE) were observed in the over-distention group, compared to that in the control group. Significant improvement in ICI and VE was seen in the ADRC treatment group in comparison with the over-distention group. The over-distention group showed significantly weaker bladder contractile responses to carbachol and electrical field stimulation than the control group, while bladder contractile responses were significantly stronger in the ADRC treatment group than that in the over-distention group. The over-distention group showed substantial fibrosis of the bladder compared to the control group, whereas bladder fibrosis was alleviated in the ADRC treatment group. In conclusion, the injection of ADRC into bladder wall improved bladder dysfunction and histological changes induced by bladder over-distention. ADRCs-based regenerative therapy could be novel treatment for DU.