Transplantation of Human Urine-Derived Stem Cells Transfected with Pigment Epithelium-Derived Factor to Protect Erectile Function in a Rat Model of Cavernous Nerve Injury

Abstract

The aim of this study was to investigate whether intracavernous injection of urine-derived stem cells (USCs) or USCs genetically modified with 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. USCs were cultured from the urine of six 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, USC, and 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 intracavernous injection with PBS, USCs, USCs, or 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. The USC and 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 USCs was associated with an increased number of nNOS-positive fibers within the penile dorsal nerves, improved expression of endothelial markers (CD31 and eNOS) and a smooth muscle marker (smoothelin), an enhanced smooth muscle to collagen ratio, decreased expression of transforming growth factor-β1 (TGF-β1), and decreased cell apoptosis in the cavernous tissue. The paracrine effect of USCs and 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.

Therapeutic Potential of Human Adipose-Derived Stem Cell Exosomes in Stress Urinary Incontinence – An in Vitro and in Vivo Study

“…Reelin (RELN) is a large secreted extracellular matrix glycoprotein that helps regulate processes related to neuronal migration. Pigment epithelium-derived factor (PEDF) displays neurotrophic functions, and a previous study has reported that PEDF could protect against the neurogenic destruction of erectile function [40]. Therefore, these results support our hypothesis that the proteins contained in exosomes could effectively facilitate skeletal muscle and peripheral nerve regeneration by stimulating related signaling pathways.…”

Exosomes derived from mesenchymal stem cells exert therapeutic effect in a rat model of cavernous nerves injury

“…Various stem cells, such as adipose tissue‐derived stem cells, bone marrow‐derived mesenchymal stem cells, muscle‐derived stem cells, urine‐derived stem cells, have been proved to effectively improve the cavernous nerve (CN) injury‐induced erectile dysfunction (Woo et al ., ; Jeon et al ., ; Martinez‐Salamanca et al ., ; Yang et al ., ). The underlying mechanisms are not still clear now.…”

Long‐term therapeutic effect of cell therapy on improvement in erectile function in a rat model with pelvic neurovascular injury

“…While the exact mechanism of action of the stem cells is still debated, two major schools of thought exist , namely a differentiation and a trophic effect. The current most accepted hypothesis involves the release of trophic factors from the cells that produce an environment favourable for local regeneration .…”

“…Mesenchymal stem cells (MSCs) are most commonly used in the treatment of ED, mainly from three sources: adult, perinatal, and foetal tissues. Adipose‐derived stem cells (ADSCs) , bone marrow‐derived stem cells, urine‐derived stem cells , placental stem cells, umbilical vein endothelial cells (UVECs), and amniotic fluid‐derived stem cells (AFSCs), have shown some level of improvement in ED models. Although each stem cell population has been separately evaluated in various short‐(2 weeks) or middle‐term (4–6 weeks) pre‐clinical in vivo experiments, one important question should be addressed: whether each stem cell population from different sources achieves similar outcomes for the recovery of erectile function in a severe ED model after long‐term follow‐up?…”