With the ever-increasing burden of urological diseases, the need for developing novel imaging biomarkers and therapeutics to manage these disorders has never been greater. Extracellular vesicles (EVs) are natural membranous nanoparticles and widely applied in both diagnostics and therapeutics for many diseases. A growing body of research has demonstrated that EVs can be engineered to enhance their efficiency, specificity, and safety. We systematically examine the strategies for achieving targeted delivery of EVs as well as the techniques for engineering them in this review, with a particular emphasis on cargo loading and transportation. Additionally, this review highlights and summarizes the wide range of imaging biomarkers and therapeutic applications of engineered EVs in the context of urological diseases, emphasizing the potential applications in urological malignancy and kidney diseases.

For patients with prostate cancer (PCa), pelvic lymph node (LN) metastasis remains a major poor prognostic factor associated with cancer-specific mortality. VEGF-C is a major lymphangiogenic ligand that plays a vital role in LN metastasis in PCa. However, in some PCa caseswith LN metastasis,VEGF-C is not upregulated, indicating that some VEGF-C-independent mechanisms are essential for lymphangiogenesis.Herein, we confirmed that extracellular vesicles (EVs) derived from PCa cells could promote LN metastasis in PCa independent of VEGF-C. We identified an EV circular RNA, circPDLIM5, that could promote lymphangiogenesis and lymphatic metastasis in both PCa cell lines and mouse models. Mechanistically, the packaging of circPDLIM5 into EVs was regulated by heterogeneous nuclear ribonucleoprotein A2B1. Subsequently, EVs were transmitted to human lymphatic endothelial cells, and EVs carrying circPDLIM5 could then directly interact with the transcription factor Yin Yang 1 to enhance the expression of Prospero homeobox 1, which is crucial for the formation, differentiation, and maturation of lymphatic vessels. Our findingshighlight the importance of a molecular mechanism mediated by EVs carrying circPDLIM5that is involved in lymphangiogenesis and LN metastasis in PCa; as a result, EVscarrying circPDLIM5 may be an attractive therapeutic target for LN-metastatic PCa.

Objective: Robot-assisted simple prostatectomy (RASP) is increasingly used as a surgical treatment option for large benign prostatic hyperplasia (BPH) (>80 mL). However, there is no sufficient expert consensus or guidelines to guide clinical practice. We aimed to obtain expert opinions for RASP for large BPH. Methods: A systematic review of the literature was performed in April 2024 using the PubMed, Embase, and Web of Science databases. Search terms were combined to construct the following search strings: (robotic) AND (simple OR benign) AND (prostatectomy). Search results were filtered by language (English only), species (human), and publication type (original article). This study used a two-phase modified Delphi approach. Results: In this expert consensus, some frequently used RASP techniques, including robot-assisted retropubic prostatectomy, robot-assisted transvesical prostatectomy, and robot-assisted urethra-sparing prostatectomy, are described. RASP offers a short learning curve for surgeons with experience in robotic surgery. Severe complications are rare in patients who undergo RASP. Conclusion: RASP technique can be recommended as a safe and effective minimally invasive treatment for symptomatic BPH patients with large prostate glands.

To construct a urine extracellular vesicle long non-coding RNA (lncRNA) classifier that can detect high-grade prostate cancer (PCa) of grade group 2 or greater and estimate the risk of progression during active surveillance, we identify high-grade PCa-specific lncRNAs by combined analyses of cohorts from TAHSY, TCGA, and the GEO database. We develop and validate a 3-lncRNA diagnostic model (Clnc, being made of AC015987.1, CTD-2589M5.4, RP11-363E6.3) that can detect high-grade PCa. Clnc shows higher accuracy than prostate cancer antigen 3 (PCA3), multiparametric magnetic resonance imaging (mpMRI), and two risk calculators (Prostate Cancer Prevention Trial [PCPT]-RC 2.0 and European Randomized Study of Screening for Prostate Cancer [ERSPC]-RC) in the training cohort (n = 350), two independent cohorts (n = 232; n = 251), and TCGA cohort (n = 499). In the prospective active surveillance cohort (n = 182), Clnc at diagnosis remains a powerful independent predictor for overall active surveillance progression. Thus, Clnc is a potential biomarker for high-grade PCa and can also serve as a biomarker for improved selection of candidates for active surveillance.

Objective:To construct a prognostic model of Wnt associated long non-coding RNAs (LncRNAs) in papillary renal cell carcinoma (pRCC).Methods:The data for ranscriptome and clinical information of pRCC patients were obtained by The Cancer Genome Atlas (TCGA). Wnt-associated LncRNAs were selected by co-expression network analysis, COX regression, and Lasso analysis to build the risk prognosis model. In addition, the predictive performance of this model is verified by receiver operating characteristic (ROC) curves.Results:Five Wnt-associated LncRNAs (CT66, PRECSIT, AL352984.1, AC124798.1, and AC011503.2) were chosen to construct a prognostic model of pRCC. Survival analyses showed that the model have predictive validity in TCGA training group (P=0.002), testing group (P=0.013) and combined group (P<0.001). When the risk score was used as an independent prognostic indicator, the area under ROC curve (AUC) for 5-year overall survival in the combined group was 0.708, indicating acceptable predictive performance.Conclusion:The prognosis model including 5 Wnt-associated LncRNAs is helpful to evaluate the prognosis of pRCC patients.

Background We aimed to develop and validate a plasma extracellular vesicle circular RNA (circRNA)-based signature that can predict overall survival (OS) in first-line abiraterone therapy for metastatic castration-resistant prostate cancer (mCRPC) patients. Methods In total, 582 mCRPC patients undergoing first-line abiraterone therapy from four institutions were sorted by three phases. In the discovery phase, 30 plasma samples from 30 case-matched patients with or without early progression were obtained to generate circRNA expression profiles using RNA sequencing. In the training phase, differentially expressed circRNAs were examined using digital droplet PCR in a training cohort ( n = 203). The circRNA signature was constructed using a least absolute shrinkage and selection operator Cox regression to predict OS. In the validation phase, the prognostic ability of this signature was prospectively validated in two external cohorts (Cohort I, n = 183; Cohort II, n = 166). Results We developed a five-circRNA signature, based on circCEP112, circFAM13A, circBRWD1, circVPS13C and circMACROD2 , which successfully stratified patients into high-risk and low-risk groups. The prognostic ability of this signature was prospectively validated in two external cohorts ( P < 0.0001, P < 0.0001). Patients with high-risk scores had shorter OS than patients with low-risk scores. Conclusion This five-circRNA signature is a reliable predictor of OS for mCRPC patients undergoing abiraterone.

Objective:The long-term follow-up results of patients with locally advanced prostate cancer (LAPC) treated with laparoscopic extensive pelvic lymph node dissection combined with radical prostatectomy (ePLND+LRP) are still rare. This study reports 246 LAPC patients treated with ePLND+LRP from 2006 to 2020 in the Third Affiliated Hospital of Sun Yat-sen University.Methods:From October 2006 to October 2020, 246 LAPC patients with ePLND+LRP were enrolled in this study. The operation time, blood loss, duration of hospital stay and complications, oncology results, and adjuvant treatments occurred within 30 days after surgery were collected.Results:The median age was 70(65-74) years; the median PSA was 24(10-60) ng/ml. The median operation time, blood loss, and hospital stay were 217 minutes, 170 ml, and 7 days, respectively. In pathological staging, there were 28 cases (11.4%) in pT2, 117 cases (47.6%) in pT3a, 92 cases (37.4%) in pT3b, and 9 cases (3.7%) in pT4. The median number of lymph nodes dissected was 21(13-27), and the median number of positive lymph nodes was 2(1-3). 48(19.5%) and 31(12.6%) patients had positive lymph nodes and positive surgical margins. Thirty-eight(15.4%) patients experienced complications, of which 17 cases (6.9%) were classified as Clavien I, 19 cases (7.7%) were classified as Clavien II, and 2 cases (0.8%) were classified as Clavien III. The median follow-up time was 127.8 months, during the follow-up period, 23(9.3%), 219(89.0%), 59(24.0%), and 7(2.8%) patients received adjuvant radiotherapy (RT), hormone therapy (HT), and salvage lymph node dissection (sLND), salvage local treatment. The 10-year BCR-free survival and metastasis-free survival (MFS) rates were 58.5%(144/246) and 73.6%(181/246), respectively. Cancer-specific survival (CSS) and overall survival (OS) were 91.6% and 85.3%, respectively. The rate of urinary control at one year after operation was 96.7%.Conclusion:The ePLND+LRP treatment of LAPC has fewer complications and a good tumor control effect. It is safe and effective as the initial treatment of LAPC.

Circular RNAs (circRNAs) have been increasingly linked to cancer progression. However, the detailed biological functions of circRNAs in prostate cancer (PCa) remain unclear. Using high-throughput circRNA sequencing, we previously identified 18 urine extracellular vesicle circRNAs that were increased in patients with PCa compared with those with benign prostatic hyperplasia. Spearman correlation analysis of the expression levels of the 18 circRNAs between the tumor tissue and matched urine extracellular vesicles in 30 PCa patients showed that circSCAF8 had the highest R-2 (R-2 = 0.635, P < 0.001). The Cox proportional hazards regression model was used to estimate the effect of circSCAF8 on progression-free survival. The in vitro and in vivo functional experiments were implemented to investigate the effects of circSCAF8 on the phenotype of PCa. We found that the knockdown of circSCAF8 in PCa cells suppressed the proliferation, migration, and invasion ability, while overexpression of circSCAF8 had the opposite effects. Similar results were observed in vivo. In a cohort of 85 patients who had undergone radical prostatectomy, circSCAF8 expression in PCa tissues was a powerful predictor of progression-free survival (HR = 2.14, P = 0.022). Mechanistically, circSCAF8 can function by binding to both miR-140-3p and miR-335 to regulate LIF expression and activate the LIF-STAT3 pathway that leads to the growth and metastasis of PCa. Collectively, our findings demonstrate that circSCAF8 contributes to PCa progression through the circSCAF8-miR-140-3p/miR-335-LIF pathway.

To efficiently remove all recurrent lymph nodes (rLNs) and minimize complications, we developed a combination approach that consisted of 68Gallium prostate-specific membrane antigen (PSMA) ligand positron emission tomography (PET)/computed tomography (CT) and integrated indocyanine green (ICG)-guided salvage lymph node dissection (sLND) for rLNs after radical prostatectomy (RP). Nineteen patients were enrolled to receive such treatment. 68Ga-PSMA ligand PET/CT was used to identify rLNs, and 5 mg of ICG was injected into the space between the rectum and bladder before surgery. Fluorescent laparoscopy was used to perform sLND. While extensive LN dissection was performed at level I, another 5 mg of ICG was injected via the intravenous route to intensify the fluorescent signal, and laparoscopy was introduced to intensively target stained LNs along levels I and II, specifically around suspicious LNs, with 68Ga-PSMA ligand PET/CT. Next, both lateral peritonea were exposed longitudinally to facilitate the removal of fluorescently stained LNs at levels III and IV. In total, pathological analysis confirmed that 42 nodes were rLNs. Among 145 positive LNs stained with ICG, 24 suspicious LNs identified with 68Ga-PSMA ligand PET/CT were included. The sensitivity and specificity of 68Ga-PSMA ligand PET/CT for detecting rLNs were 42.9% and 96.6%, respectively. For ICG, the sensitivity was 92.8% and the specificity was 39.1%. At a median follow-up of 15 (interquartile range [IQR]: 6–31) months, 15 patients experienced complete biochemical remission (BR, prostate-specific antigen [PSA] <0.2 ng ml−1), and 4 patients had a decline in the PSA level, but it remained >0.2 ng ml−1. Therefore, 68Ga-PSMA ligand PET/CT integrating ICG-guided sLND provides efficient sLND with few complications for patients with rLNs after RP.

The aim of this study was to identify a urine extracellular vesicle circular RNA (circRNA) classifier that could detect high-grade prostate cancer (PCa) of Grade Group (GG) 2 or greater. For this purpose, we used RNA sequencing to identify candidate circRNAs from urinary extracellular vesicles from 11 patients with high-grade PCa and 11 case-matched patients with benign prostatic hyperplasia. Using ddPCR in a training cohort (n = 263), we built a urine extracellular vesicle circRNA classifier (Ccirc, containing circPDLIM5, circSCAF8, circPLXDC2, circSCAMP1, and circCCNT2), which was evaluated in two independent cohorts (n = 497, n = 505). Ccirc showed higher accuracy than two standard of care risk calculators (RCs) (PCPT-RC 2.0 and ERSPC-RC) in both the training cohort and the validation cohorts. In all three cohorts, this novel urine extracellular vesicle circRNA classifier plus RCs was statistically more predictive than RCs alone for predicting ≥ GG2 PCa. This assay, which does not require precollection digital rectal examination nor special handling, is repeatable, noninvasive, and can be easily implemented as part of the basic clinical workflow.

Recently, studies on competing endogenous RNA (ceRNA) networks have become prevalent, and circular RNAs (circRNAs) have crucial implications for the development and progression of carcinoma. However, studies relevant to metastatic prostate cancer (mPCa) are scant. This study aims to discover potential ceRNAs that may be related to the prognosis of mPCa. RNA-Seq data were obtained from the MiOncoCirc database and Gene Expression Omnibus (GEO). Differential expression patterns of RNAs were examined using R packages. Circular RNA Interactome, miRTarBase, miRDB and TargetScan were applied to predict the corresponding relation between circRNAs, miRNAs and mRNAs. The Gene Ontology (GO) annotations were performed to present related GO terms, and Gene Set Enrichment Analysis (GSEA) tools were applied for pathway annotations. Moreover, survival analysis was conducted for the hub genes. We found 820 circRNAs, 81 miRNAs and 179 mRNAs that were distinguishingly expressed between primary prostate cancer (PCa) and mPCa samples. A ceRNA network including 45 circRNAs, 24 miRNAs and 56 mRNAs was constructed. In addition, the protein-protein interaction (PPI) network was built, and 10 hub genes were selected by using the CytoHubba application. Among the 10 hub genes, survival analysis showed that ITGA1, LMOD1, MYH11, MYLK, SORBS1 and TGFBR3 were significantly connected with disease-free survival (DFS). The circRNA-mediated ceRNA network provides potential prognostic biomarkers for metastatic prostate cancer.

5522 Background: The low specificity of prostate-specific antigen (PSA) has resulted in the overdiagnosis and overtreatment of clinically indolent prostate cancer (PCa). We aimed to identify a urine exosomal circular RNA (circRNA) classifier that could detect high-grade (Gleason score [GS]7 or greater) PCa. Methods: We did a three-stage study that enrolled eligible participants, including PCa-free men, 45 years or older, scheduled for an initial prostate biopsy due to suspicious digital rectal examination findings and/or PSA levels (limit range, 2.0-20.0 ng/mL), from four hospitals in China. We used RNA sequencing and digital droplet polymerase chain reaction to identify 18 candidate urine exosomal circRNAs that were increased in 11 patients with high-grade PCa compared with 11 case-matched patients with benign prostatic hyperplasia. Using a training cohort of eligible participants, we built a urine exosomal circRNA classifier (Ccirc) to detect high-grade PCa. We then evaluated the classifier in discrimination of GS7 or greater from GS6 and benign disease on initial biopsy in two independent cohorts. We used the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) to evaluate diagnostic performance, and compared Ccirc with standard of care (SOC) (ie, PSA level, age, race, and family history). Results: Between June 1, 2016, and July 31, 2019, we recruited 356 participants to the training cohort, and 442 and 325 participants to the two independent validation cohorts. We identified a Ccirc containing five differentially expressed circRNAs (circ_0049335, circ_0056536, circ_0004028, circ_0008475, and circ_0126027) that could detect high-grade PCa. Ccirc showed higher accuracy than SOC to distinguish individuals with high-grade PCa from controls in both the training cohort and the validation cohorts. (AUC 0.831 [95% CI 0.765-0.883] vs 0.724 [0.705-0.852], P = 0.032 in the training cohort; 0.823 [0.762-0.871] vs 0.706 [0.649-0.762], P = 0.007 in validation cohort 1; and 0.878 [0.802-0.943] vs 0.785 [0.701-0.890], P = 0.021 for validation cohort 2). In all three cohorts, Ccirc had higher sensitivity (range 71.6-87.2%) and specificity (82.3-90.7%) than did SOC (sensitivity, 42.3-68.2%; specificity, 40.1-62.3%) to detect high-grade PCa. Using a predefined cut point, 202 of 767 (26.3%) biopsies would have been avoided, missing only 6% of patients with dominant pattern 4 high-risk GS 7 disease. Conclusions: Ccirc is a potential biomarker for high-grade PCa among suspicious men.

目的 晚期肾盂输尿管移行细胞癌常并发转移和输尿管壁间段肿瘤侵犯.本文报告4例肾盂输尿管移行细胞癌合并肺或输尿管旁淋巴结转移及患侧输尿管壁间段肿瘤侵犯,术前组织多学科讨论,按照多学科治疗模式联合微创手术治疗.方法 收治本院晚期上尿路移行细胞癌4例,男性3例,女性1例;平均年龄73岁;平均血尿病史10个月;3例肾盂输尿管全程侵犯,4例均有患侧输尿管壁间段肿瘤侵犯,3例肾盂输尿管周围淋巴结侵犯,1例肺转移.4例患者均行多学科联合治疗,所有患者接受新辅助治疗后均接受微创手术治疗(3例机器人辅助、1例腹腔镜辅助).选择1例肺转移和肾盂及输尿管周围淋巴结侵犯做多学科病例分析汇报.结果 4例手术均顺利完成,术后予辅助治疗,中位随访时间为33个月,4位患者健侧肾功能正常,且无肿瘤复发.结论 晚期上尿路移行细胞癌多学科治疗模式中,选择合适病例切除病灶(包括输尿管壁间段肿瘤)能有效延长患者肿瘤特异性生存率.

目的 探讨尿液Dachshund同源基因2(DACH2)测定对膀胱尿路上皮癌的诊断价值.方法 收集因可疑膀胱肿瘤需行经尿道膀胱病变切除术患者的尿液,采用放射免疫法检测尿液DACH2水平,采用受试者工作特征(ROC)曲线分析尿液DACH2水平对膀胱尿路上皮癌的诊断效能.结果 共纳入72例患者,按照术后病理结果 分为膀胱尿路上皮癌组(肿瘤组)49例、膀胱良性疾病(包括慢性膀胱炎和尿路上皮增生)组(良性组)23例.肿瘤组患者术前尿液DACH2水平高于良性组(P<0.05).肿瘤组中,高级别者术前尿液DACH2水平高于低级别者(P<0.05).尿液DACH2水平诊断膀胱尿路上皮癌的ROC曲线下面积为0.796,最佳临界值为4.05 ng/ml,此时的灵敏度和特异度分别为86.7％和83.4％.结论 尿液DACH2测定可作为早期诊断膀胱尿路上皮癌的肿瘤标志物.

目的 探讨尿液外泌体circ 0040507及其联合前列腺特异性抗原(PSA)对前列腺癌的诊断价值.方法 选择35例前列腺癌患者(前列腺癌组)和27例BPH患者(BPH组),采用第三代微滴数字PCR检测尿液外泌体circ_0040507表达水平,以前列腺活组织检查(活检)病理结果为金标准,应用受试者工作特征(ROC)曲线分析尿液外泌体circ_0040507、PSA及两者联合对前列腺癌的诊断效能.结果 前列腺癌组和BPH组尿液外泌体circ_0040507表达量分别为(8.35±5.87)copies/ml和(3.25±2.45)copies/ml,前列腺癌组尿液外泌体circ_0040507表达量高于BPH组(P < 0.001);尿液外泌体circ_0040507、PSA及两者联合诊断前列腺癌的ROC曲线下面积分别为0.767(95％CI 0.649～0.896)、0.782(95％CI 0.668～0.896)、0.851(95％CI 0.755～0.946).结论 尿液外泌体circ_0040507联合PSA诊断前列腺癌具有较好的临床价值.

目的 探讨肌层浸润性膀胱癌(MIBC)患者术前中性粒细胞淋巴细胞比值(NLR)、血小板淋巴细胞比值(PLR)和淋巴细胞单核细胞比值(LMR)与根治性膀胱切除术后预后的关系.方法 收集行根治性膀胱切除术的MIBC患者临床资料,并对患者进行随访,采用Cox单因素和多因素回归分析NLR、PLR和LMR与MIBC患者的术后无转移或复发生存率(RFS)和总体生存率(OS)的关系,分别以NLR、PLR、LMR均数为标准分为高值组与低值组,绘制生存曲线,分析NLR、PLR和LMR对MIBC患者预后的预测意义.结果 共纳入129例MIBC患者.Cox单因素及多因素回归分析均显示,MIBC患者在根治性膀胱切除术前的NLR、PLR、LMR均与术后RFS、OS有关(P均<0.05).NLR<2.40组和NLR≥2.40组、PLR<159.3组和PLR≥159.3组、LMR<3.76组和LMR≥3.76组患者生存曲线比较差异均有统计学意义(P均<0.05),其中高NLR组、高PLR组及低LMR组患者的术后RFS、OS较低.结论 MIBC患者在根治性膀胱切除术前高NLR、高PLR或低LMR提示预后不良,NLR、PLR和LMR可考虑作为评估MIBC患者预后的生物标志物.

Objective: Metastasis is the major cause of the death in patients with prostate cancer. Because of the limit of detection in metastasis of prostate cancer, a biomarker in blood which can accurately predict the metastasis of prostate cancer is in greatly needed. In this abstract, we report the biomarker in blood which can accurately detect the metastasis of prostate cancer. Material and Method: 32 patients with biopsy-diagnosed prostate cancer were enrolled in our hospital between January, 2017 to March, 2018. The serum from those patients were prepared and bone scan plus pelvic MRI were also performed. A monoclonal LCRMP4 antibody Kit was prepared for the samples detection. Accordingly, extended pelvic lymph node dissection and laparoscopic radical prostatectomy were conducted. The number of nodes and positive nodes were recorded. Results: The mean age of the patients was 71 yr, PSA 21ng/ml, Gleason Score 8 in all the cases, and cTc was T3N0M0 observed in 27 patients and T3N1M0 in 5 cases . Of 32 cases with prostate cancer who had undertaken monoclonal antibody LCRMP4 Elisa Kit tests, 14 cases were defined as localized prostate cancer and other 18 patients were reported as metastatic prostate cancer. Among those 18 cases with positive tests by LCRMP4 Elisa Kit, 5 patients had metastatic lymph node by pelvic MRI. All patients underwent extended lymph node dissection and laparoscopic radical prostatectomy. The mean number of pelvic lymph nodes was 22, mean operating time was 190 minutes and mean bleeding volume 75ml. Of 14 patients who had negative results by LCRMP4 Elisa Kit, 1 cases presented 2 positive nodes; Of 18 cases with positive finding by the Elisa Kit, 16 patients had positive pelvic nodes. All the patients underwent adjuvant ADT and PSA was lower than 0.2ng/ml in all the patients after the surgery. Conclusion: Our initial study demonstrated that LCRMP4 Elisa Kit is able to accurate detect metastasis of prostate cancer. A multicenter prospective clinical validation is warranted.

BackgroundMetastasis is the major cause of cancer‐specific death in patients with prostate cancer (PCa). We previously reported that collapsing response mediator protein‐4 (CRMP4) is a PCa metastasis‐suppressor gene and the hypermethylation in CRMP4 promoter is responsible for the transcription repression in metastatic PCa. However, the underlying mechanisms remain unknown. In this study, we aimed to investigate the role of calpain‐2 in CRMP4 promoter hypermethylation and its functional modulation in PCa metastasis.MethodsCalpain‐2 expression in PCa tissues (n = 87) and its specific mechanisms of functional modulation in CRMP4 expression via limited enzymatic cleavage was investigated. We then focused on the cooperative crosstalk of calpain‐2 and NF‐κB RelA/p65 in CRMP4 promoter methylation for the initiation of PCa metastasis. Statistical differences between groups were determined using a two‐tailed Student's t‐test. P < 0.05 indicated statistically significant.ResultsCalpain‐2 was differentially upregulated in metastatic PCa compared with localized PCa. Moreover, calpain‐2 cleaved CRMP4 into the N‐terminally fragment which promoted migration and invasion in PCa cells via nuclear translocation and activation of E2F1‐mediated DNA methyltransferase 1 (DNMT1) expression. NF‐κB RelA/p65 recruited DNMT1 to bind to and methylate CRMP4 promoter in which Serine276 phosphorylation of p65 was essential. Furthermore, CRMP4 exhibited anti‐metastatic function via inhibiting the expression of VEGFC through Semaphorin3B‐Neuropilin2 signaling.ConclusionCalpain‐2 may contribute to the promoter methylation of CRMP4 to repress its transcription, leading to the metastasis of PCa via enhancing VEGFC expression.

You have accessJournal of UrologyStem Cell Research: Stem Cell Research II1 Apr 2018MP81-18 INTRACAVERNOUS INJECTION OF BONE MARROW MESENCHYMAL STEM CELLS MODIFIED WITH PDE5-RNAI IMPROVES ERECTILE DYSFUNCTION IN AGED RATS Hengjun Xiao, Weixin Yan, Yubin Cui, Jun Chen, and Liaoyuan Li Hengjun XiaoHengjun Xiao More articles by this author , Weixin YanWeixin Yan More articles by this author , Yubin CuiYubin Cui More articles by this author , Jun ChenJun Chen More articles by this author , and Liaoyuan LiLiaoyuan Li More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2726AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To determine the effect of intracavernous injection of bone marrow mesenchymal stem cells (BMSCs) genetically modified with PDE5-RNAi on erectile dysfunction (ED) in aged rats. METHODS BMSCs collected from Sprague-Dawley (SD) male rats of six weeks were transfected with lentivirus modified with PDE5-RNAi. Sixty male SD rats were equally divided into six groups: (i) A control group of normal rats (n=10), (ii) A control group of Aged rats (n=10), (iii) A negative control group of aged rats treated with PBS (n=10), (iv) aged rats treated with BMSCs alone (n=10), (v) aged rats treated with BMSCs modified with lentivirus-PDE5-RNAi (n=10), (vi) aged rats treated with lentivirus-PDE5-RNAi (n=10). ED was screened with apomorphine (100 mg/kg). Cell injections occurred directly into the corpora cavernosa (1×106 cells). The ratio of intracavernosal pressure (ICP) to mean arterial pressure (MAP), expression of endothelial markers (such as CD31 and eNOS), smooth muscle markers (such as a-SMA and desmin), VEGF, b-FGF, Angiopoietin-1 and the relative area of smooth muscle to collagen using masson trichrome staining were assessed for each group. RESULTS Implanted BMSCs modified with PDE5-RNAi displayed a significantly raised ICP and ICP/MAP ratio (p < 0.05) compared with BMSCs and lentivirus-PDE5-RNAi alone in 14 days after intracavernous injection. Immunofluorescence staining displayed expression of CD31, eNOS and a-SMA was increased in BMSCs alone or BMSCs modified with PDE5-RNAi groups in aged rats after 2 weeks. Western blot analysis and quantitative analysis for western blot confirmed the significantly increased expression of CD31, eNOS and a-SMA (p < 0.05).VEGF, b-FGF, and Angiopoietin-1 were also significantly elevated 2 weeks following BMSCs modified with PDE5-RNAi injection (p < 0.05). After receiving intracaverous injection of BMSCs modified with PDE5-RNAi, smooth muscle cells/collagen ratio significantly increased confirmed by Masson's trichrome-staining. CONCLUSIONS These results suggest that BMSCs modified with PDE5-RNAi treatment can enhance the recovery of erectile function in aged rats. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1103-e1104 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Hengjun Xiao More articles by this author Weixin Yan More articles by this author Yubin Cui More articles by this author Jun Chen More articles by this author Liaoyuan Li More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...