National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea.
J Sex Med. 2014 Aug;11(8):1962-73. doi: 10.1111/jsm.12597. Epub 2014 Jun 5.
Erectile dysfunction (ED) is a major complication of radical prostatectomy. Men with radical prostatectomy-induced ED respond less positively to oral phosphodiesterase-5 inhibitors.
The study aims to examine whether and how stromal vascular fraction (SVF) restores erectile function in mice with cavernous nerve injury (CNI).
Twelve-week-old male C57BL/6J mice were used and the animals were distributed into five groups: sham operation group and CNI group receiving a single intracavernous injection of phosphate-buffered saline (PBS) or SVF (1 × 10(4) , 1 × 10(5) , or 3 × 10(5) cells/20 μL, respectively). SVF was isolated from epididymal adipose tissues of green fluorescence protein transgenic mice.
Two weeks after injection, erectile function was measured by cavernous nerve stimulation. The penis was stained with antibodies to platelet/endothelial cell adhesion molecule-1, phosphohistone H3, and phosphorylated endothelial nitric oxide synthase (phospho-eNOS). We also performed Western blot for angiopoietin-1 (Ang-1), vascular endothelial growth factor-A, hepatocyte growth factor, phospho-eNOS, and eNOS in the corpus cavernosum tissue.
Local delivery of SVF restored erectile function in a dose-dependent manner in CNI mice. The highest erectile response was noted at a dose of 3 × 10(5) cells, for which the response was comparable with that in the sham operation group. Local delivery of SVF significantly increased the expression of angiogenic factor proteins and induced cavernous endothelial cell proliferation and eNOS phosphorylation compared with that in the PBS-treated CNI group. SVF-induced promotion of cavernous angiogenesis and erectile function was diminished in the presence of soluble antibody to Tie2, a receptor tyrosine kinase of Ang-1.
Secretion of angiogenic factors from SVF is an important mechanism by which SVF induces cavernous endothelial regeneration and restores erectile function. These findings suggest that cavernous endothelial regeneration by using SVF may represent a promising treatment strategy for radical prostatectomy-induced ED.
勃起功能障碍（ED）是根治性前列腺切除术的主要并发症。根治性前列腺切除术引起的 ED 男性对口服磷酸二酯酶-5 抑制剂的反应较差。
本研究旨在探讨基质血管部分（SVF）是否以及如何恢复海绵体神经损伤（CNI）小鼠的勃起功能。
使用 12 周龄雄性 C57BL/6J 小鼠，将动物分为五组：假手术组和 CNI 组，分别单次海绵体内注射磷酸盐缓冲液（PBS）或 SVF（1×10(4)、1×10(5)或 3×10(5)细胞/20μL）。SVF 是从绿色荧光蛋白转基因小鼠的附睾脂肪组织中分离出来的。
注射后 2 周，通过海绵体神经刺激测量勃起功能。用血小板/内皮细胞黏附分子-1、磷酸组蛋白 H3 和磷酸化内皮型一氧化氮合酶（phospho-eNOS）抗体对阴茎进行染色。我们还对阴茎海绵体组织中的血管生成素-1（Ang-1）、血管内皮生长因子-A、肝细胞生长因子、磷酸化内皮型一氧化氮合酶和内皮型一氧化氮合酶进行了 Western blot 分析。
SVF 的局部递送以剂量依赖性方式恢复 CNI 小鼠的勃起功能。在 3×10(5)细胞剂量下观察到最高的勃起反应，其反应与假手术组相当。与 PBS 处理的 CNI 组相比，SVF 的局部递送显著增加了血管生成因子蛋白的表达，并诱导了海绵体内皮细胞增殖和 eNOS 磷酸化。在存在可溶性 Tie2 抗体（Ang-1 的受体酪氨酸激酶）的情况下，SVF 诱导的海绵体血管生成和勃起功能的促进作用减弱。
SVF 分泌的血管生成因子是 SVF 诱导海绵体内皮再生和恢复勃起功能的重要机制。这些发现表明，使用 SVF 进行海绵体内皮再生可能代表根治性前列腺切除术引起的 ED 的一种有前途的治疗策略。
