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Human Urine-Derived Stem Cells Genetically-Modified with PEDF Improve Cavernous Nerve Injury-Induced Erectile Dysfunction in a Rat Model

Login to Access Video or Poster Abstract: MP41-14
Sources of Funding: the National Natural Science Foundation of China (Nos. 81471449, and 81401197)

Introduction

The aim of this study was to investigate whether intracavernous injection of urine-derived stem cells (USCs) or USCs overexpressing pigment epithelium-derived factor (PEDF) could protect the erectile function and cavernous structure in a bilateral cavernous nerve injury-induced erectile dysfunction (CNIED) rat model._x000D_

Methods

USCs were cultured from the urine of eight healthy male donors. Seventy-five rats were randomly divided into five groups (n = 15 per group): sham, bilateral cavernous nerve (CN) crush injury (BCNI), USC, GFP-USC , and PEDF-USC groups. The sham group received only laparotomy without CN crush injury and intracavernous injection with phosphate-buffered saline (PBS). All of the other groups were subjected to BCNI and intracav- ernous injection with PBS, USCs, GFP-USCs , or GFP/PEDF-USCs , respectively. The total intracavernous pressure (ICP) and the ratio of ICP to mean arterial pressure (ICP/MAP) were recorded. The penile dorsal nerves, the endothelium, and the smooth muscle were assessed within the penile tissue.

Results

The penile dorsal nerves, the endothelium, and the smooth muscle were assessed within the penile tissue. The USC and PEDF-USC groups displayed more significantly enhanced ICP and ICP/MAP ratio (p < 0.05) 28 days after cell transplantation. Immunohistochemistry (IHC) and Western blot analysis demonstrated that the protection of erectile function and the cavernous structure by PEDF-USC was associated with an increased number of nNOS-positive fibers within the penile dorsal nerves, improved expression of endothelial markers (CD31 and eNOS) and smoothelin, an enhanced smooth muscle to collagen ratio, decreased expression of TGF-b1, and decreased cell apoptosis in the cavernous tissue.

Conclusions

The paracrine effect of USCs and PEDF-USCs prevented the destruction of erectile function and the cavernous structure in the CNIED rat model by nerve protection, thereby improving endothelial cell function, increasing the smooth muscle content, and decreasing fibrosis and cell apoptosis in the cavernous tissue.

Funding

the National Natural Science Foundation of China (Nos. 81471449, and 81401197)

Authors
Qiyun Yang
Xin Chen
Tao Zheng
Kai Xia
Xiangzou Sun
Guihua Liu
Yuanyuan Zhang
Chunhua Deng
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