Many reports have shown that stem cell therapy is useful for stress urinary incontinence or interstitial cystitis.[1] However, cell therapy has many hurdles, including immunoreactivity, unexpected mal-differentiation, embolization, complications of maintenance and culture cells, and high cost. In addition, many reports have shown that paracrine effects are important for improvement.[1] Here, we focused on the contents of stem cells that have the potential to solve these problems and made filtered adipose-derived stem cell lysate (FADSCL). In this study, we investigated whether FADSCL was useful using a hydrochloric acid (HCl)-induced rat model of cystitis.

Rat adipose-derived stem cells (ADSCs) were collected from the subcutaneous fat of a rats. Cultured ADSCs (passage 3 or 4) were collected and fixed in PBS (1x10^7 cells/1 mL PBS). Then, the cells were crushed by freeze-thaw, and the filtrate (FADSCL) was collected. Eight-week-old female Fisher 344 rats were divided into (1) sham+vehicle (n=10), (2) HCl+vehicle (n=11), and (3) HCl+FADSCL (n=9) groups. On the first day (day one), saline or 1 M HCl (250 μL/body) were intravesically administered from a transurethral catheter. The next day (day two), PBS as vehicle or FADSCL (250 μL/body) were intravesically administered from a transurethral catheter. Cystometrograms were performed on day eight to evaluate intercontraction intervals (ICIs) and maximum voiding pressure (MP) in each group. Bladder weight and bladder morphology were evaluated by hematoxylin and eosin staining. Analysis of variance and Bonferroni multiple t-tests were performed for statistical analysis.

Representative cystometrogram charts are shown in Figure 1A. ICIs in the HCl+PBS group were significantly shorter than those in the sham+PBS group (P < 0.01), while the ICIs of the HCl+FADSCL group were significantly longer than those of the HCL+PBS group (P < 0.01) (Figure 1B). The maximum voiding pressure did not change among the three groups (Figure 1C). The bladder weight/body ratio did not change among the three groups. Bladder structure was not changed significantly among the three groups on day eight.

These data suggested that FADSCL might be useful for treating cystitis. This HCl-induced model is used as a hemorrhagic cystitis or interstitial cystitis model, suggesting that FADSCL may be useful in these conditions. It is very important that improvement was obtained by local administration (intravesical infusion) only once. However, this study has two limitations. First, this model is a chemical model and does not purely reflect clinical conditions. Second, the mechanisms responsible for this improvement are unknown. Further research is needed on these points.

FADSCL improved frequent urinary symptoms in rats with HCl-induced cystitis, suggesting that intravesical injection of FADSCL may be a useful treatment for hemorrhagic cystitis or interstitial cystitis.

Nat Rev Urol. 2019;16(6):363-375.