Abstract
PurposeDedifferentiated fat (DFAT) cells are mature adipocyte-derived multipotent cells that can be applicable to cell-based therapy for stress urinary incontinence (SUI). This study developed a persistence SUI model that allows long-term evaluation using a combination of vaginal distention (VD) and bilateral ovariectomy (OVX) in rats. Then, the therapeutic effects of DFAT cell transplantation in the persistence SUI model was examined.MethodsIn total, 48 Sprague–Dawley rats were divided into four groups and underwent VD (VD group), bilateral OVX (OVX group), VD and bilateral OVX (VD + OVX group), or sham operation (Control group). At 2, 4, and 6 weeks after injury, leak point pressure (LPP) and histological changes of the urethral sphincter were evaluated. Next, 14 rats undergoing VD and bilateral OVX were divided into two groups and administered urethral injection of DFAT cells (DFAT group) or fibroblasts (Fibroblast group). At 6 weeks after the injection, LPP and histology of the urethral sphincter were evaluated.ResultsThe VD + OVX group retained a decrease in LPP with sphincter muscle atrophy at least until 6 weeks after injury. The LPP and urethral sphincter muscle atrophy in the DFAT group recovered better than those in the fibroblast group.ConclusionsThe persistence SUI model was created by a combination of VD and bilateral OVX in rats. Urethral injection of DFAT cells inhibited sphincter muscle atrophy and improved LPP in the persistence SUI model. These findings suggest that the DFAT cells may be an attractive cell source for cell-based therapy to treat SUI.
Highlights
Stress urinary incontinence (SUI) is a major health problem defined as the involuntary leakage of urine under stress conditions
Dedifferentiated fat (DFAT) cells are adipose-derived stem cells (ADSCs)-like multipotent cells that are generated from mature adipocytes by an in vitro dedifferentiation strategy known as ceiling culture
To explore the therapeutic potential of DFAT cells for SUI, we evaluated the effects of DFAT cell transplantation in the persistent SUI model induced by vaginal distension (VD) and bilateral OVX
Summary
Stress urinary incontinence (SUI) is a major health problem defined as the involuntary leakage of urine under stress conditions. Compared to ADSCs, DFAT cells consist of a higher homogeneous cell population and can be expanded from a smaller amount of adipose tissue regardless of the donor’s age [7, 8]. These characteristic features indicate that the cells are expected to be applicable to autologous cell-based therapy for a variety of diseases including SUI. Our research group reported that local transplantation of DFAT cells contributed to urethral sphincter regeneration with an increased leak point pressure (LPP) in a rat vaginal distension (VD)induced SUI model [9]. As the limitation of this study, the therapeutic effect could be evaluated only over a short time such as 2 weeks after cell transplantation because the VD model had short durability and recovered to normal voiding function within 4 weeks
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