Increased urethral resistance by periurethral injection of low serum cultured adipose-derived mesenchymal stromal cells in rats

Objectives: To evaluate the effects of a periurethral injection of low serum cultured adipose tissue-derived mesenchymal stromal cells (LASC) and to develop a new autologous cell therapy for stress urinary incontinence. Methods: F344 rats were divided into three groups as based on the periurethral injection of LASC, GAX collagen or vehicle (control). At 2 and 4weeks after injection, leak point pressure (LPP) was measured before and after transection of the pelvic nerves. For cell tracking, LASC of green fluorescent protein transgenic rats were injected into nude rats. Results: At 2weeks, both the LASC and collagen groups showed significantly higher LPP than the control group. At 4weeks, the increase in LPP in the LASC group remained, whereas LPP in the collagen group decreased to baseline levels. In the absence of the urethral closure reflex after transection of the pelvic nerves, LPP in the LASC group was significantly higher than that in the other two groups. Histologically, the size of the urethral lumen was smaller in the LASC group than the collagen group. At 4weeks, most of the LASC were positive for myogenic antigens including α-smooth muscle actin, desmin and calponin I. Conclusions: Periurethral injection of autologous LASC capable of myogenic differentiation made a greater contribution to the increase in urethral resistance than did the conventional collagen bulk injection. Thus, its use for treatment of stress urinary incontinence can be postulated.