Neurogenic erectile dysfunction (NED) caused by pelvic floor surgeries/radiation therapies and associated with Parkinsons disease and diabetes remains a challenging healthcare issue. To facilitate NED research we have developed in vitro and in vivo experimental models. The in vitro model comprises the isolation, culture and treatment of rat major pelvic ganglia (MPG), which then produce outgrowing neurites whose length and molecular composition are indicative of the neurotrophic effect of the treatment agent. Through this approach we have confirmed that the brain-derived neurotrophic factor (BDNF) promotes nerve regeneration by activating the JAK/STAT signaling pathway. This has been further established by our in vivo model, which involves the transection or cruch of cavernous nerves and treatment with BDNF.
Animals ; Disease Models, Animal ; Erectile Dysfunction ; physiopathology ; Ganglia ; physiopathology ; Humans ; In Vitro Techniques ; Male ; Nerve Regeneration ; Pelvis ; innervation ; Penis ; innervation ; physiopathology

Stem cells (SCs) are undifferentiated cells that are capable of self-renewal and differentiation and that therefore contribute to the renewal and repair of tissues. Their capacity for division, differentiation, and tissue regeneration is highly dependent on the surrounding environment. Several preclinical and clinical studies have utilized SCs in urological disorders. In this article, we review the current status of SC use in benign urological diseases (erectile dysfunction, Peyronie disease, infertility, and urinary incontinence), and we summarize the results of the preclinical and clinical trials that have been conducted.
Erectile Dysfunction/physiopathology/*therapy ; Female ; Humans ; Male ; Outcome Assessment (Health Care) ; Stem Cell Transplantation/*methods ; Urinary Incontinence/physiopathology/*therapy

In regard to erectile function, Yin is flaccidity and Yang erection. In the past decade, research has mostly focused on the Yang aspect of erectile function. However, in recent years, the Yin side is attracting increasingly greater attention. This is due to the realization that penile flaccidity is no less important than penile erection and is actively maintained by mechanisms that play critical roles in certain types of erectile dysfunction (ED); for example, in diabetic patients. In addition, there is evidence that the Yin and Yang signaling pathways interact with each other during the transition from flaccidity to erection, and vice versa. As such, it is important that we view erectile function from not only the Yang but also the Yin side. The purpose of this article is to review recent advances in the understanding of the molecular mechanisms that regulate the Yin and Yang of the penis. Emphasis is given to the Rho kinase signaling pathway that regulates the Yin, and to the cyclic nucleotide signaling pathway that regulates the Yang. Discussion is organized in such a way so as to follow the signaling cascade, that is, beginning with the extracellular signaling molecules (e.g., norepinephrin and nitric oxide) and their receptors, converging onto the intracellular effectors (e.g., Rho kinase and protein kinase G), branching into secondary effectors, and finishing with contractile molecules and phosphodiesterases. Interactions between the Yin and Yang signaling pathways are discussed as well.
Erectile Dysfunction ; Humans ; Male ; Penile Erection

AIMTo identify proteins that are differentially expressed in cells derived from normal and diseased tunica albuginea (TA) as related to Peyronie's disease (PD).

METHODSCells with characteristics of fibroblasts were isolated from two tissue sources. Those from the plaque of patients with PD were designated as PT cells, and those from the normally-appearing TA of the same patients were designated as NT cells. Messenger RNAs of these cells were analyzed by real-time polymerase chain reaction (RT-PCR) for the expression of monocyte chemoattractant protein 1 (MCP-1). Crude protein lysates were analyzed by surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS) with IMAC30-Cu, CM10, and H50 chips. Each lysate was then separated into six fractions, which were further analyzed by SELDI-MS.

RESULTSRT- PCR analysis showed that PT cells expressed higher levels of MCP-1 than their counterpart NT cells. SELDI-MS analysis showed that the crude protein lysates of all four cell strains produced similar and reproducible protein profiles on IMAC30-Cu and CM10 chips. Additional SELDI-MS analyses with the fractionated lysates detected three proteins of 11.6 kDa, 14.5 kDa, 22.6 kDa that were upregulated in PT cells and two proteins of 6.3 kDa and 46.9 kDa that were downregulated in PT cells.

CONCLUSIONMCP-1, which is often involved in tissue fibrosis, was expressed at higher levels in PT than that in NT cells. Five potential biomarkers for PD were identified by SELDI-MS analysis.

Base Sequence ; Biomarkers ; analysis ; Cells, Cultured ; Chemokine CCL2 ; metabolism ; DNA Primers ; Humans ; Male ; Mass Spectrometry ; methods ; Penile Induration ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo demonstrate molecular insight into the pathology of Peyronie's disease (PD). A preliminary profile of differential gene expression between the PD plaque and control tunica albuginea was obtained with DNA microarrays. Also, to investigate the effect of intervention in PD cells, transforming growth factor-beta1 (TGF-beta1) was recruited to treat PD cell lines.

METHODSThree PD plaques and control tunica albugineas were constructed and studied. cDNA probes were prepared from RNA isolated from those cells and hybridized with the Clontech Atlas 3.6 Array. Relative changes of greater than 2.0 defined up-regulation and down-regulation, respectively. The expression of selected individual gene MCP-1 and the effect of TGF-beta1 on MCP-1 were analyzed by reverse transcriptase-polymerase chain reaction.

RESULTSSome up-regulated genes in the PD plaque detected by the Clontech assay were screened, one of them was monocyte chemotactic protein. One involved the pathogenesis of PD as a downstream gene and responded to the TGF-beta1 treatment but not CTGF. The results were also confirmed by TR-PCR in all the types of cell.

CONCLUSIONSThe cell lines from plaque tissue and normal tunica from men with PD were successfully established. The findings indicate a potential role for MCP-1 over expression in the pathogenesis of PD as a downstream gene regulated by some genes and could be a new therapeutic target in PD. The information may allow a better understanding of the basic mechanisms involved in the etiology and pathogenesis of PD. Furthermore, it may permit some strategies of therapeutic interventions combine routine methods with Chinese herbal medicine.

Cell Line ; Chemokine CCL2 ; Gene Expression ; drug effects ; Gene Expression Profiling ; Humans ; Male ; Oligonucleotide Array Sequence Analysis ; Penile Induration ; drug therapy ; genetics ; pathology ; Proteins ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transforming Growth Factor beta ; pharmacology

Stem cells hold great promise for regenerative medicine because of their ability to self-renew and to differentiate into various cell types. Although embryonic stem cells (BSC) have greater differentiation potential than adult stem cells, the former is lagging in reaching clinical applications because of ethical concerns and governmental restrictions. Bone marrow stem cells (BMSC) are the best-studied adult stem cells (ASC) and have the potential to treat a wide variety of diseases, including erectile dysfunction (ED) and male infertility. More recently discovered adipose tissue-derived stem cells (ADSC) are virtually identical to bone marrow stem cells in differentiation and therapeutic potential, but are easier and safer to obtain, can be harvested in larger quantities, and have the associated benefit of reducing obesity. Therefore, ADSC appear to be a better choice for future clinical applications. We have previously shown that ESC could restore the erectile function of neurogenic ED in rats, and we now have evidence that ADSC could do so as well. We are also investigating whether ADSC can differentiate into Leydig, Sertoli and male germ cells. The eventual goal is to use ADSC to treat male infertility and testosterone deficiency.
Adult Stem Cells ; Animals ; Cell Transplantation ; Embryonic Stem Cells ; Erectile Dysfunction ; therapy ; Humans ; Infertility, Male ; therapy ; Male ; Research