Comprehensive Research Facilities for Advanced Medical Science, Research Center for Advanced Medical Science, Dokkyo Medical University, Tochigi, Japan.
Department of Urology, Continence Center, Dokkyo Medical University, Tochigi, Japan; Department of Gastroenterological Surgery, Dokkyo Medical University, Tochigi, Japan.
Surgery. 2022 Oct;172(4):1093-1101. doi: 10.1016/j.surg.2022.06.015. Epub 2022 Aug 14.
The adipose stromal vascular fraction contains abundant mesenchymal stem cells and is utilized for cell therapy of male stress urinary incontinence. The purpose of this paper was to explore the effect of local transplantation of the stromal vascular fraction on improvement of damaged anal sphincter function.
A rat model of vaginal distension was used as a model of damaged anal sphincter function. The adipose stromal vascular fraction was separated from the inguinal fat of syngeneic green fluorescent protein transgenic rats and delivered into the internal anal sphincter of vaginal distension rats. The maximum resting pressure was evaluated during insertion and withdrawal of the catheter at 4 or 10 days after vaginal distension treatment to estimate anal sphincter function. Green fluorescent protein-transfected human-adipose-derived mesenchymal stem cells were transplanted into the internal anal sphincter of nude rats. Hematoxylin-eosin and Masson trichrome staining were performed to evaluate tissue damage and collagen synthesis. Transplanted cells were identified using a green fluorescent protein antibody and a human-specific antibody. Activation of the transplanted human-ADSC was evaluated by quantitative RT-PCR RESULTS: The mean maximum resting pressure (during catheter withdrawal) of vaginal distension rats was significantly lower than that of control rats, and stromal vascular fraction injection normalized it 4 days after treatment (control: 5.66 ± 0.98, vaginal distension: 4.04 ± 1.28, vaginal distension + stromal vascular fraction: 5.92 ± 1.28 [mmHg, control versus vaginal distension: P = .039; vaginal distension versus vaginal distension + stromal vascular fraction: P = .007]). Histological examination showed that vaginal distension disrupted the internal anal sphincter, and the transplanted syngeneic stromal vascular fraction survived for 10 days. Transplanted xenogeneic human-adipose-derived mesenchymal stem cells survived in the internal anal sphincter of nude rats for 4 and 10 days. Genes related to extracellular remodeling were up-regulated in the transplanted human-adipose-derived mesenchymal stem cells CONCLUSION: Syngeneic and heterotopic transplanted adipose-derived mesenchymal stem cells engrafted in the internal anal sphincter and ameliorated damaged anal sphincter function in a rat model of vaginal distension.
脂肪基质血管成分富含间充质干细胞，可用于治疗男性压力性尿失禁的细胞疗法。本文旨在探讨局部移植基质血管成分对受损肛门括约肌功能的改善作用。
采用阴道扩张大鼠模型作为肛门括约肌功能受损模型。从同基因 GFP 转基因大鼠腹股沟脂肪中分离出脂肪基质血管成分，并将其递送至阴道扩张大鼠的肛门内括约肌。在阴道扩张治疗后 4 或 10 天，评估导管插入和拔出时的最大静息压力，以评估肛门括约肌功能。将转染 GFP 的人脂肪源性间充质干细胞移植到裸鼠的肛门内括约肌。行苏木精-伊红和 Masson 三色染色评估组织损伤和胶原合成。用 GFP 抗体和人特异性抗体鉴定移植细胞。通过定量 RT-PCR 评估移植人 ADSC 的激活情况。
阴道扩张大鼠的平均最大静息压力（导管拔出时）明显低于对照组，基质血管成分注射可在治疗后 4 天使压力恢复正常（对照组：5.66±0.98，阴道扩张组：4.04±1.28，阴道扩张+基质血管成分组：5.92±1.28[mmHg]，对照组与阴道扩张组：P=0.039；阴道扩张组与阴道扩张+基质血管成分组：P=0.007）。组织学检查显示，阴道扩张破坏了肛门内括约肌，移植的同基因基质血管成分可存活 10 天。异种移植的人脂肪源性间充质干细胞可在裸鼠的肛门内括约肌中存活 4 天和 10 天。移植的人脂肪源性间充质干细胞中与细胞外重塑相关的基因上调。
同基因和异基因移植的脂肪源性间充质干细胞在阴道扩张大鼠模型中植入肛门内括约肌，并改善受损的肛门括约肌功能。
