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利用人羊膜间充质干细胞(hAFSCs)的再生作用,在双侧海绵体神经挤压(BCNC)损伤大鼠模型中恢复勃起功能。

Harnessing the regenerative effects of human amniotic stem cells (hAFSCs) on restoring erectile function in a bilateral cavernous nerve crush (BCNC) injury rat model.

机构信息

Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei City, 231403, Taiwan.

School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, 242062, Taiwan.

出版信息

Stem Cell Res Ther. 2024 Nov 5;15(1):400. doi: 10.1186/s13287-024-03972-1.

DOI:10.1186/s13287-024-03972-1
PMID:39501401
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11539709/
Abstract

BACKGROUND

Intracavernous (IC) injections of stem cells has been shown to ameliorate cavernous nerve (CN)-induced erectile dysfunction (ED). However, the regenerative effects underlying the recovery of erectile function (EF) in human amniotic fluid-derived stem cells (hAFSCs) remain unclear. In the bilateral cavernous nerve crushing (BCNC) injury rat paradigm, we sought to ascertain the effects of hAFSC treatment on EF recovery during the incipient phase.

METHODS

Three groups of 45 male rats were used in this study: sham (Group 1), saline IC injection after BCNC (Group 2), and hAFSC intracavernous injection (ICI) after BCNC (Group 3). hAFSCs from the fourth passage showed potential to differentiate into trilineage cells. All animals were subjected to EF analysis on the 28th day post-injection and tissues were retrieved for histopathological and immunohistochemical analyses.

RESULTS

IC injections of hAFSC significantly improved EF parameters in BCNC-ED rats at 28 days post-injury. AFSC treatment enhanced the smooth muscle condition and increased the smooth muscle/collagen ratio, as evidenced by histological analysis. Immunohistology revealed increased expression of 𝛼-SMA andvWf in the corpus cavernosum and enhanced expression of nNOS in the dorsal penile nerve in BCNC-ED rats (p < 0.05). Western blotting showed that hAFSC treatment significantly increased α-SMA expression in the hAFSC group compared with that in the BCNC group. Electron microscopy revealed significantly elevated myelination in the CN (p < 0.05), maintenance of smooth muscle structures, and restoration of EF in BCNC-ED rats treated with hAFSC.

DISCUSSION AND CONCLUSIONS

hAFSC treatment increased EF in BCNC-ED rats at a single dose. As BCNC-ED resembles ED caused by radical prostatectomy (RP), this therapy has high potential for ED patients after RP surgery.

摘要

背景

已有研究表明,海绵体内(IC)注射干细胞可改善海绵体神经(CN)诱导的勃起功能障碍(ED)。然而,人羊膜源性干细胞(hAFSCs)恢复勃起功能(EF)的再生作用尚不清楚。在双侧海绵体神经挤压(BCNC)损伤大鼠模型中,我们试图确定 hAFSC 治疗对早期 EF 恢复的影响。

方法

本研究使用了三组 45 只雄性大鼠:假手术组(第 1 组)、BCNC 后生理盐水 IC 注射组(第 2 组)和 BCNC 后 hAFSC IC 注射组(第 3 组)。第 4 代 hAFSC 显示出向三系细胞分化的潜能。所有动物均在注射后第 28 天进行 EF 分析,并取回组织进行组织病理学和免疫组织化学分析。

结果

BCNC-ED 大鼠 IC 注射 hAFSC 可显著改善 EF 参数。AFSC 治疗增强了平滑肌状况,增加了平滑肌/胶原比,组织学分析证实了这一点。免疫组织化学显示,BCNC-ED 大鼠海绵体中 𝛼-SMA 和 vWf 的表达增加,背神经中 nNOS 的表达增强(p<0.05)。Western blot 显示,与 BCNC 组相比,hAFSC 组的 α-SMA 表达显著增加。电镜显示,hAFSC 治疗组大鼠 CN 有髓化程度显著升高(p<0.05),维持平滑肌结构,恢复 BCNC-ED 大鼠的 EF。

讨论和结论

单次 hAFSC 治疗可提高 BCNC-ED 大鼠的 EF。由于 BCNC-ED 类似于根治性前列腺切除术(RP)引起的 ED,因此这种治疗方法对 RP 手术后的 ED 患者具有很高的潜力。

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