Department of Urology, Faculty of Medicine, University of Kyrenia, Mersin, Turkey.
Department of Pharmacology, Faculty of Pharmacy, Cukurova University, Adana, Turkey.
J Sex Med. 2021 May;18(5):889-899. doi: 10.1016/j.jsxm.2021.02.005. Epub 2021 Mar 27.
Effects of human umbilical cord blood (HUCB) as a valuable source for stem cell-based therapies have not been studied in persistent post-5-alpha reductase inhibitors (5ARI) erectile dysfunction (PPED).
To determine the effect of intracavernosal injection of HUCB mononuclear cells (MNCs) on ED associated with dutasteride treatment.
Twenty five adult male Sprague-Dawley rats were divided into 5 groups (n = 5 per group): (i) control, (ii) 8-week dutasteride (0.5 mg/kg/day, in drinking water), (iii) 12-week dutasteride, (iv) 8-week dutasteride+HUCB-MNCs (1 × 10) and (v) 12-week dutasteride+HUCB-MNCs. HUCB-MNCs were administered intracavernosally after eight weeks of dutasteride treatment. Experiments were performed at 4 weeks following the injection of HUCB-MNCs. Erectile responses and isometric tension of corpus cavernosum (CC) were measured. The protein expressions of phosphodiesterase type 5 (PDE5), endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS), hypoxia-inducible factor (HIF)-1α and smooth muscle/collagen contents in penile tissue were evaluated by Western blotting, immunohistochemistry, and Masson's trichrome staining, respectively.
In vivo erectile function, in vitro relaxant and contractile responses of CC, protein expression and localization of PDE5, eNOS, nNOS, HIF-1α, and smooth muscle content in penile tissue.
Erectile responses in the dutasteride-treated groups were significantly decreased compared with controls (P < .001), persisting after 4-wk of washout. HUCB-MNCs restored diminished intracavernosal pressure responses, acetylcholine-, sodium nitroprusside-, sildenafil-induced relaxations, and increased phenylephrine and electrical field stimulation (EFS)-induced contractions. Decreased EFS-induced relaxations in dutasteride-treated groups were not restored by HUCB-MNCs. Increased PDE5 and reduced nNOS expressions in dutasteride groups were restored by HUCB-MNCs in the 12-week dutasteride group. eNOS and HIF-1α protein expression and serum total and free testosterone levels were similar among groups. HUCB-MNCs reversed the decreased smooth muscle/collagen ratio in dutasteride-treated tissues. There was a significant increase in PDE5 and HIF-1α staining in 8-week dutasteride animals.
This study demonstrates the corrective potential of HUCB-MNCs on some persistent structural and functional deterioration caused by 5ARI treatment in rats, which may encourage further evaluation of HUCB-MNCs in men with PPED.
Therapeutic application of intracavernosal HUCB-MNCs is a novel approach for the rat model of post-5ARI ED. Lack of serum and tissue dihydrotestosterone measurements, vehicle injections and characterization of the cells remain limitations of our study.
The persistent ED after prolonged administration of dutasteride in rats is reversed by HUCB-MNC treatment, which holds promise as a realistic therapeutic modality for this type of ED. Oztekin CV, Yilmaz-Oral D, Kaya-Sezginer E, et al. Beneficial Effects of Human Umbilical Cord Blood Mononuclear Cells on Persistent Erectile Dysfunction After Treatment of 5-Alpha Reductase Inhibitor in Rats. J Sex Med 2021;18:889-899.
人脐血（HUCB）作为干细胞治疗的有价值来源的作用尚未在持续性 5α-还原酶抑制剂（5ARI）后勃起功能障碍（PPED）中进行研究。
确定经尿道内注射 HUCB 单核细胞（MNC）对 dutasteride 治疗相关 ED 的影响。
将 25 只成年雄性 Sprague-Dawley 大鼠分为 5 组（每组 n = 5）：（i）对照组，（ii）8 周 dutasteride（0.5mg/kg/天，在饮用水中），（iii）12 周 dutasteride，（iv）8 周 dutasteride+HUCB-MNC（1×10）和（v）12 周 dutasteride+HUCB-MNC。在 dutasteride 治疗 8 周后经尿道内注射 HUCB-MNC。HUCB-MNC 注射后 4 周进行实验。测量阴茎海绵体（CC）的勃起反应和等长张力。通过 Western blot、免疫组织化学和 Masson 三色染色分别评估阴茎组织中磷酸二酯酶 5（PDE5）、内皮型一氧化氮合酶（eNOS）、神经元型一氧化氮合酶（nNOS）、缺氧诱导因子（HIF）-1α和平滑肌/胶原含量的蛋白表达。
体内勃起功能、CC 的体外松弛和收缩反应、阴茎组织中 PDE5、eNOS、nNOS、HIF-1α和平滑肌含量的蛋白表达和定位。
与对照组相比， dutasteride 治疗组的勃起反应明显下降（P <.001），洗脱 4 周后仍持续。HUCB-MNC 恢复了降低的海绵体内压反应、乙酰胆碱、硝普钠、西地那非诱导的松弛作用，并增加了苯肾上腺素和电刺激（EFS）诱导的收缩作用。HUCB-MNC 未恢复 dutasteride 治疗组中 EFS 诱导的松弛作用减少。HUCB-MNC 恢复了 12 周 dutasteride 组中增加的 PDE5 和减少的 nNOS 表达。各组的 eNOS 和 HIF-1α 蛋白表达和血清总睾酮和游离睾酮水平相似。HUCB-MNC 逆转了 dutasteride 治疗组织中平滑肌/胶原比例的降低。在 8 周 dutasteride 动物中，PDE5 和 HIF-1α 染色显著增加。
本研究表明，HUCB-MNC 对大鼠 5ARI 治疗引起的一些持续性结构和功能恶化具有纠正潜力，这可能鼓励进一步评估 HUCB-MNC 在 PPED 男性中的应用。
经尿道内注射 HUCB-MNC 是大鼠 5ARI 后 ED 模型的一种新的治疗方法。缺乏血清和组织二氢睾酮测量、载体注射和细胞特征仍然是我们研究的局限性。
在大鼠中延长 dutasteride 给药后持续存在的 ED 通过 HUCB-MNC 治疗得到逆转，这为这种类型的 ED 提供了一种现实的治疗方法。
