Department of Urology, Nihon University School of Medicine, Tokyo, Japan.
Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo, 173-8610, Japan.
Int Urol Nephrol. 2022 Apr;54(4):789-797. doi: 10.1007/s11255-021-03083-3. Epub 2022 Feb 17.
Dedifferentiated 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.
In 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.
The 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.
The 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.
去分化脂肪（DFAT）细胞是成熟脂肪细胞来源的多能细胞，可应用于压力性尿失禁（SUI）的细胞治疗。本研究建立了一种持久性 SUI 模型，通过阴道扩张（VD）和双侧卵巢切除术（OVX）的联合应用，在大鼠中进行长期评估。然后，研究了 DFAT 细胞移植在持久性 SUI 模型中的治疗效果。
共 48 只 Sprague-Dawley 大鼠分为 4 组，分别进行 VD（VD 组）、双侧 OVX（OVX 组）、VD 和双侧 OVX（VD+OVX 组）或假手术（对照组）。在损伤后 2、4 和 6 周，评估漏点压（LPP）和尿道括约肌的组织学变化。然后，将 14 只接受 VD 和双侧 OVX 的大鼠分为两组，分别进行尿道注射 DFAT 细胞（DFAT 组）或成纤维细胞（Fibroblast 组）。在注射后 6 周，评估 LPP 和尿道括约肌的组织学。
VD+OVX 组至少在损伤后 6 周内保持 LPP 降低和括约肌萎缩。DFAT 组的 LPP 和尿道括约肌肌肉萎缩恢复情况优于成纤维细胞组。
通过 VD 和双侧 OVX 在大鼠中建立了持久性 SUI 模型。尿道注射 DFAT 细胞抑制了括约肌萎缩，并改善了持久性 SUI 模型中的 LPP。这些发现表明，DFAT 细胞可能是治疗 SUI 的细胞治疗有吸引力的细胞来源。
