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Adipose tissue-derived stem cells (ADSCs) are a somatic stem cell population contained in fat tissue that may be utilized in the treatment of urologic disease. ADSCs are excellent candidates for these therapies as they are easily obtained in large quantities from adipose tissue, and possess the potential to undergo long-term proliferation, self-renewal and multipotent differentiation. We reviewed the available evidence from 1964 through 2014 concerning ADSC availability, differentiation, and potentiality in the context of treatment forurologic diseases.

Mesenchymal stem cells (MSCs) exist in most adult tissues and have been located near or within blood vessels. Although "perivascular" has been commonly used to describe such locations, increasing evidence points at the vessel wall as the exact location. Thus, "vascular stem cells (VSCs)" is recommended as a more accurate term for MSCs. Furthermore, 2 cell populations, namely pericytes and adventitial progenitor cells (APCs), are the likely VSCs. The pericyte evidence relies on the so-called pericyte-specific markers, but none of these markers is pericyte specific. In addition, pericytes appear to be too functionally diverse and sophisticated to have a large differentiation capacity. On the other hand, APCs are more naïve functionally and, therefore, more akin to being VSCs. In vitro, these cells spontaneously differentiate into pericytes, and can be induced to differentiate into vascular cells (endothelial and smooth muscle cells) and mesenchymal cells (e.g., bone, cartilage, and fat). In vivo, indirect evidence also points to their ability to differentiate into mesenchymal cells of their native tissue (e.g., fat). Moreover, they possess a large paracrine capacity and, therefore, can help maintain tissue homeostasis by encouraging the replication and differentiation of mesenchymal cells locally. These proposed in vivo functions are areas of interest for future research on VSCs.

Both clinical and preclinical studies have mostly shown beneficial effects for Phosphodiesterase-5 (PDE-5) inhibitors in the treatment of lower urinary tract symptoms. Molecular studies have consistently shown abundant PDE-5 expression in bladder smooth muscle. Data concerning urethral PDE-5 expression have been surprising because striated muscle was not only positively identified, but also found to express more PDE-5 than the smooth muscle. In the prostate, highly variable results have been obtained. For PDE-5 expression, the data have ranged from extremely low to highly abundant. PDE-5 has been found in the glandular epithelium, vascular smooth muscle, endothelium, and fibromuscular stroma.

AimTo develop a clinically applicable MRI technique for tracking stem cells in matrix-associated stem-cell implants, using the US FDA-approved iron supplement ferumoxytol.Materials & methodsFerumoxytol-labeling of adipose-derived stem cells (ADSCs) was optimized in vitro. A total of 11 rats with osteochondral defects of both femurs were implanted with ferumoxytol- or ferumoxides-labeled or unlabeled ADSCs, and underwent MRI up to 4 weeks post matrix-associated stem-cell implant. The signal-to-noise ratio of different matrix-associated stem-cell implant was compared with t-tests and correlated with histopathology.ResultsAn incubation concentration of 500 µg iron/ml ferumoxytol and 10 µg/ml protamine sulfate led to significant cellular iron uptake, T2 signal effects and unimpaired ADSC viability. In vivo, ferumoxytol- and ferumoxides-labeled ADSCs demonstrated significantly lower signal-to-noise ratio values compared with unlabeled controls (p < 0.01). Histopathology confirmed engraftment of labeled ADSCs, with slow dilution of the iron label over time.ConclusionFerumoxytol can be used for in vivo tracking of stem cells with MRI.

Priapism is a rare condition that involves persistent penile erection for greater than 4 h. Distinct variants exist, each with unique characteristics. Ischemic priapism is a painful medical emergency that may occur as a result of veno-occlusion leading to hypoxia and tissue death. Recurrent bouts of ischemic priapism, or stuttering priapism, require treatment for individual attacks as well as long-term prevention. Non-ischemic priapism is associated with trauma and may be managed conservatively. Recent advances into the pathophysiology of priapism have allowed the development of treatment algorithms that specifically target the mechanisms involved. In this review, we outline the basics of smooth muscle contraction and describe how derangement of these pathways results in priapism. A pathophysiological approach to the treatment of priapism is proposed with duration-based algorithms presented to assist in management.

The intricate anatomy of the corpus cavernosum in both the flaccid and tumescent state has not been fully elucidated. We report our experience using a three-dimensional (3D) scanner to reconstruct cadaveric casts and compare them with 3D images of two prototypes of penile prosthesis. Two different models of the Titan Coloplast inflatable penile prosthesis were analyzed using a 3D scanner. The first was the standard model and the second was a newer model with a rounder silicone tip. Two cadaveric phalluses were harvested using Smooth-Cast 300Q polyurethane molding. The molds were excised and scanned along side the penile prosthesis. 3D scans were completed and analyzed using Leios Mesh software, and GOM Inspect software. The 3D scans demonstrated the mean human corporal radii 2 mm from the distal tip to be 36.51 mm (36.01-37.0 mm), which is an obtuse angle. The standard Titan penile prosthesis spherical radius at the same level was 202.52 mm, while the new silicone tip prosthesis had a radius of 139.33 mm. 3D mapping further demonstrated the trajectory of the cavernosa appeared curvilinear and the distal ends appeared blunt. The use of cadaveric cavernosal molds in combination with the 3D scanner allowed us to accurately image the corpus cavernosum for the first time. Our findings suggest that anatomically accurate corporal tips appear to be relatively blunt and that the new Titan silicone tip penile prosthesis more closely resembles the human corporal tip.

The prevailing school of thought is that mesenchymal stromal cells (MSC) do not express CD34, and this sets MSC apart from hematopoietic stem cells (HSC), which do express CD34. However, the evidence for MSC being CD34(-) is largely based on cultured MSC, not tissue-resident MSC, and the existence of CD34(-) HSC is in fact well documented. Furthermore, the Stro-1 antibody, which has been used extensively for the identification/isolation of MSC, was generated by using CD34(+) bone marrow cells as immunogen. Thus, neither MSC being CD34(-) nor HSC being CD34(+) is entirely correct. In particular, two studies that analyzed CD34 expression in uncultured human bone marrow nucleated cells found that MSC (BMSC) existed in the CD34(+) fraction. Several studies have also found that freshly isolated adipose-derived MSC (ADSC) express CD34. In addition, all of these ADSC studies and several other MSC studies have observed a disappearance of CD34 expression when the cells are propagated in culture. Thus the available evidence points to CD34 being expressed in tissue-resident MSC, and its negative finding being a consequence of cell culturing.

Mesenchymal stem cells (MSCs) are well known for their immunomodulatory capabilities. In particular, their immunosuppressive property is believed to permit their allogeneic or even xenogeneic transplantation into immunocompetent recipients without the use of immunosuppressants. Adipose-derived stem cell (ADSC), owing to its ease of isolation from an abundant tissue source, is a promising MSC for the treatment of a wide range of diseases. ADSC has been shown to lack major histocompatibility complex-II expression, and its immunosuppressive effects mediated by prostaglandin E2. Both preclinical and clinical studies have shown that allogeneic transplantation of ADSCs was able to control graft-versus-host disease. In regard to xenotransplantation a total of 27 preclinical studies have been published, with 20 of them performed with the investigators' intent. All 27 studies used ADSCs isolated from humans, possibly due to the wide availability of lipoaspirates. On the other hand, the recipients were mouse in 13 studies, rat in 11, rabbit in 2, and dog in 1. The targeted diseases varied greatly but all showed significant improvements after ADSC xenotransplantation. For clinical application in human medicine, ADSC xenotransplantation offers no obvious advantage over autotransplantation. But in veterinary medicine, xenotransplantation with porcine ADSC is a practical alternative to the costly and inconvenient autotransplantation.

PurposeTo develop a clinically applicable imaging technique for monitoring differential migration of macrophages into viable and apoptotic matrix-associated stem cell implants (MASIs) in arthritic knee joints.Materials and methodsWith institutional animal care and use committee approval, six athymic rats were injected with intravenous ferumoxytol (0.5 mmol iron per kilogram of body weight) to preload macrophages of the reticuloendothelial system with iron oxide nanoparticles. Forty-eight hours later, all animals received MASIs of viable adipose-derived stem cells (ADSCs) in an osteochondral defect of the right femur and mitomycin-pretreated apoptotic ADSCs in an osteochondral defect of the left femur. One additional control animal each received intravenous ferumoxytol and bilateral scaffold-only implants (without cells) or bilateral MASIs without prior ferumoxytol injection. All knees were imaged with a 7.0-T magnetic resonance (MR) imaging unit with T2-weighted fast spin-echo sequences immediately after, as well as 2 and 4 weeks after, matrix-associated stem cell implantation. Signal-to-noise ratios (SNRs) of viable and apoptotic MASIs were compared by using a linear mixed-effects model. MR imaging data were correlated with histopathologic findings.ResultsAll ADSC implants showed a slowly decreasing T2 signal over 4 weeks after matrix-associated stem cell implantation. SNRs decreased significantly over time for the apoptotic implants (SNRs on the day of matrix-associated stem cell implantation, 2 weeks after the procedure, and 4 weeks after the procedure were 16.9, 10.9, and 6.7, respectively; P = .0004) but not for the viable implants (SNRs on the day of matrix-associated stem cell implantation, 2 weeks after the procedure, and 4 weeks after the procedure were 17.7, 16.2, and 15.7, respectively; P = .2218). At 4 weeks after matrix-associated stem cell implantation, SNRs of apoptotic ADSCs were significantly lower than those of viable ADSCs (mean, 6.7 vs 15.7; P =

PurposeTo determine factors associated with students' comfort in addressing patients' sexuality in the clinical context.MethodThe authors invited students enrolled in MD-degree-granting and osteopathic medical schools in the United States and Canada to participate in an anonymous Internet survey between February and July 2008. The survey assessed ethnodemographic factors and sexual history. Respondents also completed the Center for Epidemiologic Studies Depression Scale. Male respondents completed the International Index of Erectile Function and the Premature Ejaculation Diagnostic Tool. Female respondents completed the Female Sexual Function Index and the Index of Sex Life. The authors used descriptive statistics, ANOVA, and multivariable logistic regression to analyze responses.ResultsThe authors' analyses included 2,261 completed survey responses: 910 from men, 1,343 from women, and 8 from individuals who self-identified as "other" gendered. Over 53% of respondents (n = 1,206) stated that they felt they had not received sufficient training in medical school to address sexual concerns clinically. Despite this, 81% of students (n = 1,827) reported feeling comfortable dealing with their patients' sexuality issues. Students with limited sexual experience, students at risk for sexual problems, and students who felt that they had not been trained adequately were less likely to report being comfortable talking to patients about sexual health issues.ConclusionsPerception of inadequate sexuality training in medical school and personal issues pertaining to sex may be associated with students' difficulty in addressing patients' sexuality. Adequate training is preeminently associated with feeling comfortable addressing patients' sexuality and should be a priority for medical education.

BackgroundRNA activation (RNAa) is a newly discovered mechanism of gene activation triggered by small double-stranded RNAs termed 'small activating RNAs' (saRNAs). Thus far, RNAa has only been demonstrated in human cells and is unclear whether it is conserved in other mammals.Methodology/principal findingsIn the present study, we evaluated RNAa in cells derived from four mammalian species including nonhuman primates (African green monkey and chimpanzee), mouse, and rat. Previously, we identified saRNAs leading to the activation of E-cadherin, p21, and VEGF in human cells. As the targeted sequences are highly conserved in primates, transfection of each human saRNA into African green monkey (COS1) and chimpanzee (WES) cells also resulted in induction of the intended gene. Additional saRNAs targeting clinically relevant genes including p53, PAR4, WT1, RB1, p27, NKX3-1, VDR, IL2, and pS2 were also designed and transfected into COS1 and WES cells. Of the nine genes, p53, PAR4, WT1, and NKX3-1 were induced by their corresponding saRNAs. We further extended our analysis of RNAa into rodent cell types. We identified two saRNAs that induced the expression of mouse Cyclin B1 in NIH/3T3 and TRAMP C1 cells, which led to increased phosphorylation of histone H3, a downstream marker for chromosome condensation and entry into mitosis. We also identified two saRNAs that activated the expression of CXCR4 in primary rat adipose-derived stem cells.Conclusions/significanceThis study demonstrates that RNAa exists in mammalian species other than human. Our findings also suggest that nonhuman primate disease models may have clinical applicability for validating RNAa-based drugs.

Selection of optimal quality embryos for in vitro fertilization (IVF) transfer is critical to successful live birth outcomes. Currently, embryos are chosen based on subjective assessment of morphologic developmental maturity. A non-invasive means to quantitatively measure an embryo's developmental maturity would reduce the variability introduced by the current standard. We present a method that exploits the scaling electrical properties of pre-transfer embryos to quantitatively discern embryo developmental maturity using light-induced dielectrophoresis (DEP). We show that an embryo's DEP response is highly correlated with its developmental stage. Uniquely, this technique allows one to select, in sequence and under blinded conditions, the most developmentally mature embryos among a mixed cohort of morphologically indistinguishable embryos cultured in optimized and sub-optimal culture media. Following assay, embryos continue to develop normally in vitro. Light-induced dielectrophoresis provides a non-invasive, quantitative, and reproducible means to select embryos for applications including IVF transfer and embryonic stem cell harvest.

ObjectiveTo investigate whether oestrogen, selective oestrogen receptor modulators (SERMs), and growth hormone (GH) can prevent the development of voiding dysfunction in a postpartum postmenopausal rat model of voiding dysfunction.Materials and methodsImmediately after spontaneous delivery, nine primiparous Sprague-Dawley rats served as uninjured controls (sham group) and 54 underwent intravaginal balloon dilation. On day 7, the 54 subject rats underwent bilateral ovariectomy. A week later, six treatment groups of nine rats were randomized to receive: normal saline (injured control group), 17beta-oestradiol (E(2)), raloxifene, levormeloxifene, GH, or GH + E(2). The treatment groups received daily subcutaneous injections for 3 weeks. The effects of hormone treatment were examined by conscious cystometry at the end of the study. Voiding dysfunction was defined to include overactive bladder and sphincter deficiency.ResultsThe sham rats had a mean (sd) voiding frequency of 3 (0.87) times in 10 min and a bladder capacity of 0.43 (0.13) mL with smooth cystometry curves. The number of rats in each treatment group (each group contained nine rats) that had voiding dysfunction was as follows: E(2), three; raloxifene, six; levormeloxifene, four; and controls, four (P > 0.05 among the groups). Only one rat in the GH-treated group and no rats in the GH + E(2)-treated group had voiding dysfunction, which was significantly less in the GH + E(2)-treated group than in the controls (P = 0.041).ConclusionThis functional data suggest that the development of voiding dysfunction can be prevented by short-term administration of GH and GH + E(2) in our rat model. SERMs and E(2) alone seem to have no therapeutic effect.