Restoration of erectile function with intracavernous injections of endothelial progenitor cells after bilateral cavernous nerve injury in rats
Restoration of erectile function with intracavernous injections of endothelial progenitor cells after bilateral cavernous nerve injury in rats
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DOI：
10.1111/andr.12085
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发表时间：
2015-09-01
期刊：
影响因子：
4.5
通讯作者：
Chiang, H. -S.
中科院分区：
文献类型：
--
作者：
Liao, C. -H.;Wu, Y. -N.;Chiang, H. -S.
内皮祖细胞是一种骨髓来源的内皮细胞，具有循环、增殖和分化为成熟内皮细胞的能力。循环内皮祖细胞可以在一定程度上被募集到损伤部位，并且它们的应用可以促进受损组织的修复或内皮化。研究海绵体内注射内皮祖细胞对双侧海绵体神经损伤所致勃起功能障碍(ED)大鼠的影响。总体而言，24只雄性SD大鼠被随机分为三组：假手术组、仅给药组或EPC治疗组。内皮祖细胞治疗组和单纯赋形剂组大鼠分别在海绵体注射内皮祖细胞或赋形剂前造成双侧CN损伤。术后4周测量最大海绵体内压(ICP)、最大海绵体内压变化、海绵体曲线下面积、海绵体内最大内压变化与平均动脉压的比值(MAP；Delta ICP/MAP)，评价勃起功能。对阴茎组织中神经型一氧化氮合酶(NNOS)、神经丝蛋白-1(NF-1)、血管性假血友病因子(VWF)、内皮型一氧化氮合酶(ENOS)的表达及平滑肌细胞含量进行组织形态计量学分析。与假手术组和EPC治疗组相比，单纯用药组的最大颅内压和勃起功能的所有其他功能参数均显著降低(均P<；0.001)。与假手术组和EPC治疗组相比，仅使用赋形剂的大鼠血管内皮细胞含量减少(P<；0.01)。EPC治疗组大鼠背动脉vWF和eNOS的表达明显高于单纯赋形剂组(p<；0.05)。总之，EPC治疗通过向背动脉募集内皮祖细胞和保留海绵体中的平滑肌细胞，恢复了双侧CN损伤大鼠的勃起功能。这些发现阐明了内皮祖细胞治疗人类勃起功能障碍的治疗潜力。
Endothelial progenitor cells (EPCs) are bone marrow-derived endothelial cells capable of circulating, proliferating, and differentiating into mature endothelial cells. Circulating EPCs can be directly recruited to some extent at sites of injury, and their administration could accelerate repair or endothelialization of the damaged tissue. We investigated the effects of intracavernous injections of EPCs into the corpora cavernosa of rats with erectile dysfunction (ED) caused by bilateral cavernous nerve (CN) injury. Overall, 24 male Sprague-Dawley rats were randomized into three groups: sham surgery, vehicle-only, or EPC treatment. Rats in the EPC treatment and vehicle-only groups were subjected to bilateral CN injury before injection of EPCs or vehicle, respectively, into the corpora cavernosa. Four weeks after surgery, erectile function was assessed by measuring maximum intracavernosal pressure (ICP), change in ICP, area under the ICP curve, and ratio of change in ICP and mean arterial pressure (MAP; Delta ICP/MAP). Penile tissue was histomorphometrically analyzed for the expression of neural nitric oxide synthase (nNOS), neurofilament-1 (NF-1), von Willebrand factor (vWF), endothelial NOS (eNOS), and smooth muscle cell content. Maximum ICP and all other functional parameters of erectile function were significantly reduced in the vehicle-only group vs. the sham and EPC treatment groups (all p < 0.001). Smooth muscle cell content was decreased in the vehicle-only vs. the sham and EPC treatment groups (both p < 0.01). Expressions of vWF and eNOS in the dorsal artery were significantly higher in the EPC treatment than the vehicle-only group (p < 0.05). In conclusion, EPC treatment restored erectile function in a rat model of bilateral CN injury through recruitment of EPCs toward the dorsal artery and preservation of smooth muscle cells in the corpus cavernosum. These findings elucidate the therapeutic potential of EPCs for treating ED in humans.