Stem cells are undifferentiated cells that are capable of renewal and repair of tissue due to their capacity for division and differentiation. The purpose of this review is to describe recent advances in the use of stem cell (SC) therapy for male erectile dysfunction (ED). We performed a MEDLINE database search of all relevant articles regarding the use of SCs for ED. We present a concise summary of the scientific principles behind the usage of SC for ED. We discuss the different types of SCs, delivery methods, current pre-clinical literature, and published clinical trials. Four clinical trials employing SC for ED have been published. These articles are summarized in this review. All four report improvements in ED after SC therapy. SC therapy remains under investigation for the treatment of ED. It is reassuring that clinical trials thus far have reported positive effects on erectile function and few adverse events. Safety and methodical concerns about SC acquisition, preparation and delivery remain and require continued investigation prior to wide-spread application of these methods.
Erectile Dysfunction* ; Humans ; Male ; Methods ; Stem Cells

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

Advances in the neurobiology of growth factors, neural development, and prevention of cell death have resulted in a heightened clinical interest for the development of protective and regenerative neuromodulatory strategies for the cavernous nerves (CNs), as therapies for prostate cancer and other pelvic malignancies often result in neuronal damage and debilitating loss of sexual function. Nitric oxide released from the axonal end plates of these nerves within the corpora cavernosa causes relaxation of smooth muscle, initiating the haemodynamic changes of penile erection as well as contributing to maintained tumescence; the loss of CN function is primarily responsible for the development of erectile dysfunction (ED) after pelvic surgery and serves as the primary target for potential neuroprotective or regenerative strategies. Evidence from pre-clinical studies for select neuromodulatory approaches is reviewed, including neurotrophins, glial cell line-derived neurotrophic factors (GDNF), bone morphogenic proteins, immunophilin ligands, erythropoetin (EPO), and stem cells.
Animals ; Bone Morphogenetic Proteins ; therapeutic use ; Brain-Derived Neurotrophic Factor ; therapeutic use ; Erectile Dysfunction ; drug therapy ; etiology ; therapy ; Erythropoietin ; therapeutic use ; Glial Cell Line-Derived Neurotrophic Factor ; therapeutic use ; Growth Differentiation Factor 5 ; Humans ; Immunophilins ; Male ; Nerve Growth Factors ; therapeutic use ; Neurotransmitter Agents ; therapeutic use ; Penis ; innervation ; Peripheral Nerve Injuries ; Postoperative Complications ; Stem Cell Transplantation

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

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

Low-intensity pulsed ultrasound (LIPUS) is a promising therapy that has been increasingly explored in basic research and clinical applications. LIPUS is an appealing therapeutic option as it is a noninvasive treatment that has many advantages, including no risk of infection or tissue damage and no known adverse reactions. LIPUS has been shown to have many benefits including promotion of tissue healing, angiogenesis, and tissue regeneration; inhibition of inflammation and pain relief; and stimulation of cell proliferation and differentiation. The biophysical mechanisms of LIPUS remain unclear and the studies are ongoing. In recent years, more and more research has focused on the relationship between LIPUS and stem/progenitor cells. A comprehensive search of the PubMed and Embase databases to July 2020 was performed. LIPUS has many effects on stem cells. Studies show that LIPUS can stimulate stem cells in vitro; promote stem cell proliferation, differentiation, and migration; maintain stem cell activity; alleviate the problems of insufficient seed cell source, differentiation, and maturation; and circumvent the low efficiency of stem cell transplantation. The mechanisms involved in the effects of LIPUS are not fully understood, but the effects demonstrated in studies thus far have been favorable. Much additional research is needed before LIPUS can progress from basic science research to large-scale clinical dissemination and application.
Cell Proliferation ; Humans ; Signal Transduction ; Stem Cells/radiation effects* ; Ultrasonic Therapy/methods* ; Ultrasonic Waves