The aim of this study was to determine the possibility of improving erectile dysfunction using cell therapy with either human urine-derived stem cells (USCs) or USCs genetically-modified with FGF2 in a type 2 diabetic rat model. Human USCs were collected from 3 healthy donors. USCs were transfected with FGF2 (USCs-FGF2). Sixty-five SD male rats were divided into five groups (G). A control group of normal rats (G1, n = 10), and four other test groups of type 2 diabetic erectile dysfunction rats: PBS as a negative control (G2, n = 10), USCs (G3, n = 15), lentivirus-FGF2 (G4, n = 15), and USCs-FGF2 (G5, n = 15). Diabetes was induced in the rats via a high fat diet for 28 days and a subsequent intraperitoneal injection of streptozotocin (35 mg/kg). Erectile dysfunction was screened with apomorphine (100 μg/kg). Cell injections in the test groups (G2–G5) occurred directly into the corpora cavernosa. The implanted cells were tracked at 7 days (n = 5 animals/G) and 28 days (n = 10 animals/G) post injection. Mean arterial pressure (MAP), intracavernosal pressure (ICP), expression of endothelial markers (CD31, VEGF and eNOS), smooth muscle markers (desmin and smoothelin), histological changes and erectile function were assessed for each group. USCs expressed mesenchymal stem cell markers, and secreted a number of proangiogenic growth factors. USCs expressed endothelial cell markers (CD31 and vWF) after transfection with FGF2. Implanted USCs or USCs-FGF2 displayed a significantly raised ICP and ICP/MAP ratio (p<0.01) 28 days after intracavernous injection. Although few cell were detected within the implanted sites, histological and western blot analysis demonstrated an increased expression of endothelial and smooth muscle markers within the cavernous tissue following USC or USC-FGF2 injection. The paracrine effect of USCs or USCs-FGF2 induced improvement of erectile function in type 2 diabetic rats by recruiting resident cells and increasing the endothelial expression and contents of smooth muscle.
The aim of this study was to determine whether adipose derived stem cells (ADSCs) expressing vascular endothelial growth factor (VEGF) gene can improve endothelial function, recover the impaired VEGF signaling pathway and enhance smooth muscle contents in a rat diabetic erectile dysfunction (DED) model. DED rats were induced via intraperitoneal injection of streptozotocin (40 mg/kg), and then screened by apomorphine (100 µg/kg). Five groups were used (n = 12/group)–Group 1 (G1): intracavernous injection of lentivirus-VEGF; G2: ADSCs injection; G3: VEGF-expressing ADSCs injection; G4: Phosphate buffered saline injection; G1–G4 were DED rats; G5: normal rats. The mean arterial pressure (MAP) and intracavernosal pressure (ICP) were measured at days 7 and 28 after the injections. The components of the VEGF system, endothelial, smooth muscle, pericytes markers in cavernoursal tissue were assessed. On day 28 after injection, the group with intracavernosum injection of ADSCs expressing VEGF displayed more efficiently and significantly raised ICP and ICP/MAP (p<0.01) than those with ADSCs or lentivirus-VEGF injection. Western blot and immunofluorescent analysis demonstrated that improved erectile function by ADSCs-VEGF was associated with increased expression of endothelial markers (VEGF, VEGF R1, VEGF R2, eNOS, CD31 and vWF), smooth muscle markers (a-actin and smoothelin), and pericyte markers (CD146 and NG2). ADSCs expressing VEGF produced a therapeutic effect and restored erectile function in diabetic rats by enhancing VEGF-stimulated endothelial function and increasing the contents of smooth muscle and pericytes.
23 April 2012 in International Journal of Andrology
Summary: The purpose of this study is to investigate the possible underlying pathogenesis of erectile dysfunction(ED) in young men with low risk of coronary heart disease and no well‐known aetiology. To conduct this study, 122 patients with ED under the age of 40 were enrolled, along with 33 age‐matched normal control subjects. The patients with ED had significantly higher levels of systolic blood pressure (SBP), total cholesterol and triglyceride, high sensitivity C‐reactive protein (hs‐CRP), greater carotid intima‐media thickness (CIMT) and Framingham risk score (FRS) than the control group, though all of these values were within the respective normal range. Further, the brachial artery flow‐ mediated vasodilation (FMD) values were significantly lower in ED patients and correlated positively with the severity of ED (r = 0.714, p < 0.001). When these significant factors were studied in the multivariate logistic regression model, FMD, SBP, hs‐CRP and FRS remained the statistical significance. The receiver‐operating characteristic (ROC) analysis demonstrated that FMD had a high ability to predict ED in young male with low FRS [area under the curve (AUC) 0.921, p < 0.001]. The cutoff value of FMD <10.25% had sensitivity of 82.8% and specificity of 100% for diagnosis of ED. FRS and hs‐ CRP were also proven to be predictors of ED (AUC 0.812, p < 0.001; AUC 0.645, p = 0.011, respectively). The results of this study validated that subclinical endothelial dysfunction and low‐grade inflammation may be the underlying pathogenesis of ED with no well‐known aetiology. Young patients complaining of ED should be screened for cardiovascular risk factors and possible subclinical atherosclerosis. Measurement of FMD, hs‐CRP and FRS can improve our ability to predict and treat ED, as well as subclinical cardiovascular disease early for young male.
1 September 2014 in The Journal of Sexual Medicine
Noninvasive parameters for predicating sperm retrieval rate (SRR) are desirables. Follicle-stimulating hormone (FSH) has been an important predictor since the first years of testicular sperm extraction. Recent studies showed continuous interests in FSH, with both pros and cons. Thus, we conducted a meta-analysis to evaluate the diagnostic value of FSH as a predictor for patients with nonobstructive azoospermia (NOA) taking testicular sperm retrieval. Eligible diagnosis tests were identified from electronic databases (Cochrane Central Register of Controlled Trials, Medline, and EMBASE) without language restrictions. The database search, quality assessment, and data extraction were performed independently by two reviewers. The reference standard was the sperm retrieval result. Diagnostic value of FSH were explored by area under receiver operation characteristics (ROC) curve using Review Manager, version 5.1.0 (Cochrane Collaboration, Oxford, UK) and Meta-DiSc, version 1.4. Meta regression will be done if there is heterogeneity. Then, we find 11 tests including a total of 1350 patients met the inclusion criteria. Our pooled analysis showed that the area under ROC curve of FSH was 0.72 ± 0.04. Meta regression analyses showed that region and average age have an influence on the diagnostic value. FSH showed more diagnostic value with patients in East Asia and with younger patients. We concluded that FSH had moderate value in independently predicating SRR in men with NOA (area under curve >0.7). More detailed diagnosis tests should be anticipated in the future to confirm the diagnostic value of other noninvasive parameters.