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Peng H, Zhang H, Xin S, Li H, Liu X, Wang T, Liu J, Zhang Y, Song W. Associations between Erectile Dysfunction and Vascular Parameters: A Systematic Review and Meta-Analysis. World J Mens Health 2024; 42:712-726. [PMID: 38311372 PMCID: PMC11439810 DOI: 10.5534/wjmh.230192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 09/13/2023] [Accepted: 10/03/2023] [Indexed: 02/10/2024] Open
Abstract
PURPOSE Erectile dysfunction (ED) is associated with several vascular disorders, but the associations between ED and vascular parameters are still unclear. MATERIALS AND METHODS We analyzed and synthesized a comprehensive range of studies from PubMed, Web of Science, and Scopus regarding the associations between ED and the following measures: ankle-brachial index (ABI), pulse wave velocity (PWV), intima-media thickness (IMT), nitrate-mediated dilation (NMD), flow-mediated dilation (FMD), augmentation index (AI), endothelial progenitor cells (EPCs) and other vascular parameters. Subgroup analysis was conducted according to specific types of parameters. Study quality was assessed by using the Newcastle-Ottawa Scale. Sensitivity analysis was conducted to confirm the robustness of the pooled results. RESULTS Fifty-seven studies with 7,312 individuals were included. Twenty-eight studies were considered to be high-quality. ED patients had a 0.11 mm higher IMT (95% confidence interval [CI]: 0.07, 0.15), a 2.86% lower FMD (95% CI: -3.56, -2.17), a 2.34% lower NMD (95% CI: -3.37, -1.31), a 2.83% higher AI (95% CI: 0.02, 5.63), a 1.11 m/s higher PWV (95% CI: 0.01, 2.21), and a 0.72% lower percentage of EPCs (95% CI: -1.19, -0.24) compared to those without ED. However, ABI was similar between ED patients and non-ED individuals. According to sensitivity analysis, the pooled results were robust. CONCLUSIONS Our study confirmed the associations between ED and several vascular parameters and highlighted the importance of prevention and management of vascular and endothelial dysfunction in ED patients.
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Affiliation(s)
- Hao Peng
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- The Second Clinical School, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hanlin Zhang
- The First Clinical School, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Sheng Xin
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hao Li
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaming Liu
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Wang
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jihong Liu
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yucong Zhang
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Wen Song
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Sun T, Liu Y, Yuan P, Jia Z, Yang J. Bibliometric and Visualization Analysis of Stem Cell Therapy for Erectile Dysfunction. Drug Des Devel Ther 2024; 18:731-746. [PMID: 38476204 PMCID: PMC10929656 DOI: 10.2147/dddt.s448483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 02/24/2024] [Indexed: 03/14/2024] Open
Abstract
Purpose As a common male disease, erectile dysfunction (ED) seriously affects the physical and mental health of patients. In recent years, studies have continued to point out the great potential of stem cell therapy (SCT) in the treatment of ED. The purpose of this study is to comprehensively analyze the research of SCT for ED and understand the development trends and research frontiers in this field. Methods Publications regarding SCT and ED were retrieved and collected from the Web of Science Core Collection. CiteSpace and VOSviewer software were then utilized for bibliometric and visualization analysis. Results A total of 524 publications were eventually included in this study. The annual number of publications in this field was increasing year by year. China and the USA were the two most productive countries. Lin GT, Lue TF and Lin CS, and the University of California San Francisco where they worked were the most productive research group and institution, respectively. The journal with the largest number of publications was The Journal of Sexual Medicine, and the following were mostly professional journals of urology and andrology. Diabetes mellitus-induced ED and cavernous nerve injury-related ED were the two most commonly constructed models of ED in studies. Concerning the types of stem cells, mesenchymal stem cells derived from adipose and bone marrow were most frequently used. Moreover, future research would mainly focus on exosomes, tissue engineering technology, extracorporeal shockwave therapy, and clinical translation. Conclusion The research of SCT for ED will receive increasing global attention in the future. Our study provided bibliometric and visualization analysis of published literature, helping researchers understand the global landscape and frontiers in this field. More preclinical and clinical studies should be conducted to more deeply explore the underlying mechanisms of treatment and promote clinical translation.
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Affiliation(s)
- Taotao Sun
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China
| | - Yipiao Liu
- Department of Hepatopancreatobiliary Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China
| | - Penghui Yuan
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China
| | - Zhankui Jia
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China
| | - Jinjian Yang
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China
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Saltzman RG, Golan R, Masterson TA, Sathe A, Ramasamy R. Restorative therapy clinical trials for erectile dysfunction: a scoping review of endpoint measures. Int J Impot Res 2023; 35:720-724. [PMID: 36068326 DOI: 10.1038/s41443-022-00610-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 08/18/2022] [Accepted: 08/23/2022] [Indexed: 11/08/2022]
Abstract
Given the lack of regulatory approval for restorative therapies for the treatment of erectile dysfunction, we hypothesized that clinical trials would vary in methodology and endpoint measurements. Our objective was to analyze methodological approaches and outcome measures of clinical trials evaluating restorative therapies for erectile dysfunction. Data was extracted from clinicaltrials.gov on trials which contained the keywords "erectile dysfunction". We evaluated trials initiated between 2004 and 2021 which listed a restorative therapy intervention. We identified 95 trials investigating energy-based/shockwave therapies (60/95), stem cell therapies (25/95), platelet-based therapies (6/95), and others (4/95). Only 41.1% of the trials evaluated safety. The most common efficacy endpoint was International Index of Erectile Function and Sexual Health Inventory for Men, and only 29.5% utilized penile Doppler. Thirty (31.6%) trials had been completed yet only 3 (3.2%) have published results. We found substantial heterogeneity in methodological approach in the trials. Subjective measures of erectile function were commonly reported, but definitions of inclusion criteria and objective outcome measures were inconsistent. These results provide a basis for the design of future clinical trials to improve the quality of trial data and aid in the development of standardized criteria for erectile dysfunction clinical trials.
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Affiliation(s)
- Russell G Saltzman
- Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Roei Golan
- Florida State University College of Medicine, Tallahassee, FL, USA
| | - Thomas A Masterson
- Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Aditya Sathe
- University of Tennessee Health Science Center College of Medicine, Memphis, TN, USA
| | - Ranjith Ramasamy
- Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
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Huang RL, Li Q, Ma JX, Atala A, Zhang Y. Body fluid-derived stem cells - an untapped stem cell source in genitourinary regeneration. Nat Rev Urol 2023; 20:739-761. [PMID: 37414959 PMCID: PMC11639537 DOI: 10.1038/s41585-023-00787-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/30/2023] [Indexed: 07/08/2023]
Abstract
Somatic stem cells have been obtained from solid organs and tissues, including the bone marrow, placenta, corneal stroma, periosteum, adipose tissue, dental pulp and skeletal muscle. These solid tissue-derived stem cells are often used for tissue repair, disease modelling and new drug development. In the past two decades, stem cells have also been identified in various body fluids, including urine, peripheral blood, umbilical cord blood, amniotic fluid, synovial fluid, breastmilk and menstrual blood. These body fluid-derived stem cells (BFSCs) have stemness properties comparable to those of other adult stem cells and, similarly to tissue-derived stem cells, show cell surface markers, multi-differentiation potential and immunomodulatory effects. However, BFSCs are more easily accessible through non-invasive or minimally invasive approaches than solid tissue-derived stem cells and can be isolated without enzymatic tissue digestion. Additionally, BFSCs have shown good versatility in repairing genitourinary abnormalities in preclinical models through direct differentiation or paracrine mechanisms such as pro-angiogenic, anti-apoptotic, antifibrotic, anti-oxidant and anti-inflammatory effects. However, optimization of protocols is needed to improve the efficacy and safety of BFSC therapy before therapeutic translation.
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Affiliation(s)
- Ru-Lin Huang
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qingfeng Li
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jian-Xing Ma
- Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Anthony Atala
- Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Yuanyuan Zhang
- Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
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Li X, Yang HF, Chen Y, Pei LJ, Jiang R. Effect of the icariin on endothelial microparticles, endothelial progenitor cells, platelets, and erectile function in spontaneously hypertensive rats. Andrology 2021; 10:576-584. [PMID: 34779135 DOI: 10.1111/andr.13127] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 10/19/2021] [Accepted: 11/03/2021] [Indexed: 12/15/2022]
Abstract
OBJECTIVES To investigate the effect of icariin on endothelial microparticles, endothelial progenitor cells, platelets, and erectile function in spontaneously hypertensive rats. MATERIALS AND METHODS Twelve 8-week-old healthy male Wistar-Kyoto rats and 12 spontaneously hypertensive rats were randomly divided into four following groups: Wistar-Kyoto control group (normal saline 1 ml/d given by gavage), Wistar-Kyoto + icariin group (icariin 10 mg/kg × d dissolved in 1 ml normal saline and given by gavage), spontaneously hypertensive rats control group (normal saline 1 ml/d given by gavage), and spontaneously hypertensive rats + icariin group (icariin 10 mg/kg × d dissolved in 1 ml normal saline and given by gavage). Four weeks later, the maximum intracavernous pressure/mean arterial pressure, platelet count, mean platelet volume, platelet distribution width, endothelial microparticles, endothelial progenitor cells, and vitronectin receptor were measured in each group. RESULTS Under 3 or 5 V electrical stimulation, the maximum intracavernous pressure/mean arterial pressure in the spontaneously hypertensive rats + icariin group (0.23 ± 0.03, 0.38 ± 0.02) was significantly higher compared to the spontaneously hypertensive rats control group (0.12 ± 0.02, 0.20 ± 0.02) (p<0.05). Platelet count, mean platelet volume, and platelet distribution width in the spontaneously hypertensive rats + icariin group (1103.67 ± 107.70 × 109 /L, 9.08 ± 0.50 fl, 11.87 ± 0.45%) were significantly lower than those in the spontaneously hypertensive rats control group (1298.00 ± 89.54 × 109 /L, 9.72 ± 0.44 fl, 13.03 ± 0.59%) (all p < 0.05). Endothelial microparticles, endothelial progenitor cells, and vitronectin receptor in the spontaneously hypertensive rats + icariin group (1.01 ± 0.28%, 1.53 ± 0.65%, 2.13 ± 0.53%) were significantly lower than those in the spontaneously hypertensive rats control group (1.58 ± 0.19%, 2.71 ± 0.64%, 3.76 ± 0.52%) (all p < 0.05). Moreover, maximum intracavernous pressure/mean arterial pressure was strongly negatively correlated with platelet distribution width and vitronectin receptor (r > 0.7), and maximum intracavernous pressure/mean arterial pressure was moderately negatively correlated with mean platelet volume, endothelial microparticles, and endothelial progenitor cells (0.5 < r<0.7). CONCLUSION Icariin may improve erectile function in spontaneously hypertensive rats by reducing the content of endothelial microparticles in blood and inhibiting the activation of the platelets. Endothelial microparticles, endothelial progenitor cells, and platelet activation-related (mean platelet volume, platelet distribution width, and vitronectin receptor) can be used as indicators for icariin to improve erectile function in spontaneously hypertensive rats.
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Affiliation(s)
- Xu Li
- Department of Urology, the Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Hai-Fan Yang
- Department of Urology, the Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yong Chen
- Department of Urology, the Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Li-Jun Pei
- Department of Urology, the Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Rui Jiang
- Department of Urology, the Affiliated Hospital of Southwest Medical University, Luzhou, China
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Pan D, Xu ZH, Gao Q, Li M, Guan Y, Zhao ST. Relationship between penile erection and the ratio of estradiol to testosterone: A retrospective study. Andrologia 2020; 52:e13701. [PMID: 32539180 DOI: 10.1111/and.13701] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 04/23/2020] [Accepted: 05/16/2020] [Indexed: 12/01/2022] Open
Abstract
Previous studies have found that the ratio of estradiol to testosterone (E2/T ratio) has a negative effect on sexual function, but the relationship between the E2/T ratio and erection of the penis is not clarified. We conducted a retrospective study of 183 patients with erectile dysfunction and 52 healthy men to investigate the relationship between penis base erection and tip erection. All participants underwent nocturnal penile tumescence tests and medical history checks and had relevant biochemical and endocrine indicators measured. The ratio of estradiol to testosterone was calculated. The relationship between E2/T ratio and erectile time of penile tip and penile base was determined by univariate analysis, multivariate analysis and stratification analysis. After adjusting for mixed factors, the results showed that the E2/T ratio had a more significant negative effect on the base of the penis compared with the tip of the penis (Hazard ratio: -4.34 95% CI: -6.52, -2.16 p = .0001). Moreover, when the effective erection time was ≥10 min, the negative effect of E2/T on penile root erection was more obvious (HR ratio: -4.46 95% CI: -6.50, -2.43 p < .0001). In summary, our study demonstrated a negative relationship between E2/T ratio and penile erection, particularly at the root of the penis.
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Affiliation(s)
- Dong Pan
- Department of Urology, Shandong Provincial Hospital, Shandong, China
- Department of Urology, The Second Hospital of Shandong University, Jinan, China
| | - Zhi-He Xu
- Department of Urology, The Second Hospital of Shandong University, Jinan, China
| | - Qiang Gao
- Department of General Surgery, Taishan Medical University, Taian, China
| | - Ming Li
- Department of Urology, Shandong Provincial Hospital, Shandong, China
| | - Yong Guan
- Department of Urology, Shandong Provincial Hospital, Shandong, China
| | - Sheng-Tian Zhao
- Department of Urology, Shandong Provincial Hospital, Shandong, China
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Wen Y, Liu G, Zhang Y, Li H. MicroRNA-205 is associated with diabetes mellitus-induced erectile dysfunction via down-regulating the androgen receptor. J Cell Mol Med 2019; 23:3257-3270. [PMID: 30729682 PMCID: PMC6484320 DOI: 10.1111/jcmm.14212] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Revised: 12/12/2018] [Accepted: 01/17/2019] [Indexed: 12/15/2022] Open
Abstract
As a major class of regulatory genes in majority metazoans, microRNAs (miRs) play an important role in various diseases including diabetes mellitus (DM). Lack of androgens has previously been associated with DM-induced erectile dysfunction (DMED). In addition, the biological functioning of androgen is mediated by androgen receptor (AR). Herein, we sought to investigate whether miRs participate in AR-associated DMED. Sprague-Dawlay rats were employed to establish DMED models. After modelling, levels of miR-205 and AR in their cavernous bodies were measured. The relationship between miR-205 and AR was verified using a dual-luciferase reporter gene assay. The underlying regulatory mechanisms of miR-205 were investigated in concert with the treatment of mimics or inhibitors of miR-205, or AR overexpression in the cavernous smooth muscle cells (CSMCs) isolated from rats with DMED. Meanwhile, the effects of miR-205 and AR on cell proliferation and apoptosis were evaluated using MTT assay and flow cytometry respectively. Rats with DMED presented with increased miR-205 and decreased AR levels in the cavernous bodies. AR was identified as a target gene of miR-205. Down-regulation of miR-205 or up-regulation of AR could increase proliferation and inhibits apoptosis of CSMCs in addition to improvements in the erectile functioning of rats with DMED. In summary, miR-205 may contribute to the pathogenesis of DMED via down-regulation of AR expressions.
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Affiliation(s)
- Yan Wen
- Department of EndocrinologyChina‐Japan Union Hospital of Jilin UniversityChangchunChina
| | - Guohui Liu
- Department of CardiologyChina‐Japan Union Hospital of Jilin UniversityChangchunChina
| | - Yun Zhang
- Department of UrologyChina‐Japan Union Hospital of Jilin UniversityChangchunChina
| | - Hai Li
- Department of UrologyChina‐Japan Union Hospital of Jilin UniversityChangchunChina
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Fiuk JV, Tadros NN. Erectile dysfunction in renal failure and transplant patients. Transl Androl Urol 2019; 8:155-163. [PMID: 31080776 PMCID: PMC6503231 DOI: 10.21037/tau.2018.09.04] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2018] [Accepted: 09/10/2018] [Indexed: 12/21/2022] Open
Abstract
Erectile dysfunction (ED) is a prevalent and pertinent condition in the chronic kidney disease (CKD) population. It has a multifactorial etiology, including disruptions of the hypothalamic-pituitary-gonadal axis, the endothelial paracrine signaling system, calcium and vitamin D homeostasis, along with several other factors. Efficacy of treatment of ED in the CKD population is comparable to non-CKD patients across multiple modalities, including PDE5 inhibitors, vacuum erectile devices, intracavernosal injections and penile prostheses. Renal transplant improves the contributing comorbid conditions that lead to ED in CKD patients; thus rates of ED are improved post-transplant. It is important to note that there is a small percentage of patients with persistent ED after renal transplantation.
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Affiliation(s)
- Julia V Fiuk
- Division of Urology, Southern Illinois University School of Medicine, Springfield, IL, USA
| | - Nicholas N Tadros
- Division of Urology, Southern Illinois University School of Medicine, Springfield, IL, USA
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Drapeau C, Benson KF, Jensen GS. Rapid and selective mobilization of specific stem cell types after consumption of a polyphenol-rich extract from sea buckthorn berries ( Hippophae) in healthy human subjects. Clin Interv Aging 2019; 14:253-263. [PMID: 30787601 PMCID: PMC6368418 DOI: 10.2147/cia.s186893] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Purpose The aim of this study was to evaluate the effects of a proanthocyanidin-rich extract of sea buckthorn berry (SBB-PE) on the numbers of various types of adult stem cells in the blood circulation of healthy human subjects. Study design and methods A randomized, double-blind, placebo-controlled, cross-over trial was conducted in 12 healthy subjects. Blood samples were taken immediately before and at 1 and 2 hours after consuming either placebo or 500 mg SBB-PE. Whole blood was used for immunophenotyping and flow cytometry to quantify the numbers of CD45dim CD34+ CD309+ and CD45dim CD34+ CD309− stem cells, CD45− CD31+ CD309+ endothelial stem cells, and CD45− CD90+ mesenchymal stem cells. Results Consumption of SBB-PE was associated with a rapid and highly selective mobilization of CD45dim CD34+ CD309− progenitor stem cells, CD45− CD31+ CD309+ endothelial stem cells, and CD45− CD90+ lymphocytoid mesenchymal stem cells. In contrast, only minor effects were seen for CD45dim CD34+ CD309+ pluripotential stem cells. Conclusion Consumption of SBB-PE resulted in selective mobilization of stem cell types involved in regenerative and reparative functions. These data may contribute to the understanding of the traditional uses of SBB for preventive health, regenerative health, and postponing the aging process.
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Insights into Endothelial Progenitor Cells: Origin, Classification, Potentials, and Prospects. Stem Cells Int 2018; 2018:9847015. [PMID: 30581475 PMCID: PMC6276490 DOI: 10.1155/2018/9847015] [Citation(s) in RCA: 130] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Revised: 08/27/2018] [Accepted: 09/18/2018] [Indexed: 02/07/2023] Open
Abstract
With the discovery of endothelial progenitor cells (EPCs) in the late 1990s, a paradigm shift in the concept of neoangiogenesis occurred. The identification of circulating EPCs in peripheral blood marked the beginning of a new era with enormous potential in the rapidly transforming regenerative field. Overwhelmed with the revelation, researchers across the globe focused on isolating, defining, and interpreting the role of EPCs in various physiological and pathological conditions. Consequently, controversies emerged regarding the isolation techniques and classification of EPCs. Nevertheless, the potential of using EPCs in tissue engineering as an angiogenic source has been extensively explored. Concomitantly, the impact of EPCs on various diseases, such as diabetes, cancer, and cardiovascular diseases, has been studied. Within the limitations of the current knowledge, this review attempts to delineate the concept of EPCs in a sequential manner from the speculative history to a definitive presence (origin, sources of EPCs, isolation, and identification) and significance of these EPCs. Additionally, this review is aimed at serving as a guide for investigators, identifying potential research gaps, and summarizing our current and future prospects regarding EPCs.
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Condorelli RA, Calogero AE, La Vignera S. The importance of the functional network between endothelial microparticles and late endothelial progenitor cells for understanding the physiological aspects of this new vascular repair system. Acta Physiol (Oxf) 2018; 222. [PMID: 28771989 DOI: 10.1111/apha.12931] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- R. A. Condorelli
- Department of Clinical and Experimental Medicine; Policlinico “G. Rodolico”; University of Catania; Catania Italy
| | - A. E. Calogero
- Department of Clinical and Experimental Medicine; Policlinico “G. Rodolico”; University of Catania; Catania Italy
| | - S. La Vignera
- Department of Clinical and Experimental Medicine; Policlinico “G. Rodolico”; University of Catania; Catania Italy
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12
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Relationship between gut microbiota and type 2 diabetic erectile dysfunction in Sprague-Dawley rats. ACTA ACUST UNITED AC 2017; 37:523-530. [PMID: 28786059 DOI: 10.1007/s11596-017-1767-z] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Revised: 06/20/2017] [Indexed: 12/29/2022]
Abstract
In order to investigate the relationship between gut microbiota and type 2 diabetic erectile dysfunction (T2DED), we analyzed the characteristics of gut microbiota in the Sprague-Dawley (SD) rats with T2DED. Thirty-five SD rats were randomly divided into two groups: control group (n=15) with normal diet, and experimental group (n=20) with construction of T2D model. Faecal and serum samples were collected at 2nd and 8th week after establishment of T2D model, respectively. Faecal samples were used for analysis of gut microbiota, and serum samples for detection of trimethylamine N-oxide (TMAO), lipopolysaccharide (LPS), and inflammatory factors like interleukin-1 (IL-1), IL-2, IL-10, and monocyte chemoattractantprotein-1 (MCP-1). The main compositions of gut microbiota were Bacteroidetes, Proteobacteria and Firmicutes at the phylum level, and Oscillospira, Allobaculum, Bacteroides, Ruminococcus, SMB53, Prevotella, Coprococcus, Sutterella and Blautia at the genus level with relatively higher abundance in all SD rats. The relative abundance of Enterococcus, Corynebacterium, Aerococcus, Facklamia (opportunistic pathogens in most case) increased, and that of Allobaculum, Bifidobacterium, Eubacterium, Anaerotruncus (beneficial bacteria) decreased in T2DED group as compared with that at 2nd week after establishment of T2D model (T2D2 group). The serum contents of TMAO, LPS, IL-1, IL-2, IL-10 and MCP-1 in T2DED group were significantly higher than those in control group. The gut microbiota of T2DED rats was inhibited. The gut microbiota of T2DED rats had changed, as the relative abundance of beneficial bacterium was decreased while that of opportunistic pathogens was increased. The variations of gut microbiota might lead to inflammation and prompt the emergence of erectile dysfunction in the rats with T2D. TMAO might play an important role in the formation of T2DED.
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Cabeza de Baca T, Epel ES, Robles TF, Coccia M, Gilbert A, Puterman E, Prather AA. Sexual intimacy in couples is associated with longer telomere length. Psychoneuroendocrinology 2017; 81:46-51. [PMID: 28411413 PMCID: PMC5496682 DOI: 10.1016/j.psyneuen.2017.03.022] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Revised: 03/16/2017] [Accepted: 03/22/2017] [Indexed: 01/17/2023]
Abstract
High-quality relationships have been shown to be beneficial for physical and mental health. This study examined overall relationship satisfaction and perceived stress as well as daily reports of partner support, partner conflict, and physical intimacy obtained over the course of one week in a sample of 129 high and low stress mothers. Telomere length was examined in whole blood, as well as the two cell subpopulations: peripheral blood mononuclear cells (PBMCs) and granulocytes. Telomerase activity was measured in PBMCs. Analyses revealed no statistically significant associations of telomere length with current relationship satisfaction, daily support or conflict, or perceived stress. In contrast, women who reported any sexual intimacy during the course of the week had significantly longer telomeres measured in whole blood and PBMCs, but not in granulocytes. These relationships held covarying for age, body mass index, perceived stress, the relationship indices, and caregiver status. Sexual intimacy was not significantly related to PBMC telomerase activity. These data provide preliminary data that sexual intimacy is associated with longer telomere length. Future studies investigating these associations are warranted.
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Affiliation(s)
- Tomás Cabeza de Baca
- Department of Psychiatry, University of California, San Francisco, 3333 California St Suite 465, San Francisco, CA 94118, USA.
| | - Elissa S Epel
- Department of Psychiatry, University of California, San Francisco, 3333 California St Suite 465, San Francisco, CA 94118, USA
| | | | - Michael Coccia
- Department of Psychiatry, University of California, San Francisco, 3333 California St Suite 465, San Francisco, CA 94118, USA
| | - Amanda Gilbert
- Department of Psychiatry, University of California, San Francisco, 3333 California St Suite 465, San Francisco, CA 94118, USA
| | - Eli Puterman
- School of Kinesiology, University of British Columbia, Vancouver, BC, Canada
| | - Aric A Prather
- Department of Psychiatry, University of California, San Francisco, 3333 California St Suite 465, San Francisco, CA 94118, USA.
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14
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Xin ZC, Xu YD, Lin G, Lue TF, Guo YL. Recruiting endogenous stem cells: a novel therapeutic approach for erectile dysfunction. Asian J Androl 2016; 18:10-5. [PMID: 25926601 PMCID: PMC4736335 DOI: 10.4103/1008-682x.150040] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Transplanted stem cells (SCs), owing to their regenerative capacity, represent one of the most promising methods to restore erectile dysfunction (ED). However, insufficient source, invasive procedures, ethical and regulatory issues hamper their use in clinical applications. The endogenous SCs/progenitor cells resident in organ and tissues play critical roles for organogenesis during development and for tissue homeostasis in adulthood. Even without any therapeutic intervention, human body has a robust self-healing capability to repair the damaged tissues or organs. Therefore, SCs-for-ED therapy should not be limited to a supply-side approach. The resident endogenous SCs existing in patients could also be a potential target for ED therapy. The aim of this review was to summarize contemporary evidence regarding: (1) SC niche and SC biological features in vitro; (2) localization and mobilization of endogenous SCs; (3) existing evidence of penile endogenous SCs and their possible mode of mobilization. We performed a search on PubMed for articles related to these aspects in a wide range of basic studies. Together, numerous evidences hold the promise that endogenous SCs would be a novel therapeutic approach for the therapy of ED.
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Affiliation(s)
- Zhong-Cheng Xin
- Andrology Center, Peking University First Hospital, Peking University, Beijing 100034, USA
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15
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Liao CH, Wu YN, Lin YH, Syu Huang RF, Liu SP, Chiang HS. Restoration of erectile function with intracavernous injections of endothelial progenitor cells after bilateral cavernous nerve injury in rats. Andrology 2016; 3:924-32. [PMID: 26311341 DOI: 10.1111/andr.12085] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Revised: 05/28/2015] [Accepted: 06/29/2015] [Indexed: 01/26/2023]
Abstract
Endothelial progenitor cells (EPCs) are bone marrow-derived endothelial cells capable of circulating, proliferating, and differentiating into mature endothelial cells. Circulating EPCs can be directly recruited to some extent at sites of injury, and their administration could accelerate repair or endothelialization of the damaged tissue. We investigated the effects of intracavernous injections of EPCs into the corpora cavernosa of rats with erectile dysfunction (ED) caused by bilateral cavernous nerve (CN) injury. Overall, 24 male Sprague-Dawley rats were randomized into three groups: sham surgery, vehicle-only, or EPC treatment. Rats in the EPC treatment and vehicle-only groups were subjected to bilateral CN injury before injection of EPCs or vehicle, respectively, into the corpora cavernosa. Four weeks after surgery, erectile function was assessed by measuring maximum intracavernosal pressure (ICP), change in ICP, area under the ICP curve, and ratio of change in ICP and mean arterial pressure (MAP; ΔICP/MAP). Penile tissue was histomorphometrically analyzed for the expression of neural nitric oxide synthase (nNOS), neurofilament-1 (NF-1), von Willebrand factor (vWF), endothelial NOS (eNOS), and smooth muscle cell content. Maximum ICP and all other functional parameters of erectile function were significantly reduced in the vehicle-only group vs. the sham and EPC treatment groups (all p < 0.001). Smooth muscle cell content was decreased in the vehicle-only vs. the sham and EPC treatment groups (both p < 0.01). Expressions of vWF and eNOS in the dorsal artery were significantly higher in the EPC treatment than the vehicle-only group (p < 0.05). In conclusion, EPC treatment restored erectile function in a rat model of bilateral CN injury through recruitment of EPCs toward the dorsal artery and preservation of smooth muscle cells in the corpus cavernosum. These findings elucidate the therapeutic potential of EPCs for treating ED in humans.
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Affiliation(s)
- C H Liao
- Division of Urology, Department of Surgery, Cathay General Hospital, New Taipei City, Taiwan.,School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.,PhD Program in Nutrition & Food Science, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Y N Wu
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.,PhD Program in Nutrition & Food Science, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Y H Lin
- Graduate Institute of Basic Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - R F Syu Huang
- PhD Program in Nutrition & Food Science, Fu Jen Catholic University, New Taipei City, Taiwan
| | - S P Liu
- Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
| | - H S Chiang
- Division of Urology, Department of Surgery, Cathay General Hospital, New Taipei City, Taiwan.,School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.,PhD Program in Nutrition & Food Science, Fu Jen Catholic University, New Taipei City, Taiwan.,Graduate Institute of Basic Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
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16
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Peak TC, Anaissie J, Hellstrom WJG. Current Perspectives on Stem Cell Therapy for Erectile Dysfunction. Sex Med Rev 2016; 4:247-256. [PMID: 27871958 DOI: 10.1016/j.sxmr.2016.02.003] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Revised: 02/18/2016] [Accepted: 02/20/2016] [Indexed: 01/06/2023]
Abstract
INTRODUCTION Erectile dysfunction (ED) is a common sexual disorder that affects the lives of millions of male patients and their partners. Various medical and surgical therapies exist, with the most common being oral intake of phosphodiesterase 5 inhibitors. One therapeutic strategy in preclinical development to treat ED is stem cell transplantation. AIM To examine the studies that have investigated stem cells for the treatment of ED. METHODS A literature review was performed through PubMed focusing on stem cells and ED. MAIN OUTCOME MEASURES An assessment of different types of stem cells and how they may be applied therapeutically in the treatment of ED. RESULTS The stem cell types that have been investigated for the treatment of ED include bone marrow-derived mesenchymal, adipose-derived, muscle-derived, testes, urine-derived, neural crest, and endothelial progenitor. Depending on the cell type, research has demonstrated that with transplantation, stem cells exert a paracrine effect on penile tissue, and can differentiate into smooth muscle, endothelium, and neurons. CONCLUSION Multiple stem cell lines are currently being studied for their potential to treat ED. To date, stem cells have proven safe and effective in both animal and human models of ED. More research is needed to understand their full therapeutic potential.
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Affiliation(s)
- Taylor C Peak
- Tulane University School of Medicine, Department of Urology, New Orleans, LA, USA
| | - James Anaissie
- Tulane University School of Medicine, Department of Urology, New Orleans, LA, USA
| | - Wayne J G Hellstrom
- Tulane University School of Medicine, Department of Urology, New Orleans, LA, USA.
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17
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Hwang I, Lee HS, Yu HS, Kim ME, Lee JS, Park K. Testosterone modulates endothelial progenitor cells in rat corpus cavernosum. BJU Int 2016; 117:976-81. [DOI: 10.1111/bju.13438] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Affiliation(s)
- Insang Hwang
- Department of Urology; Chonnam National University Medical School; Sexual Medicine Research Center; Chonnam National University; Gwangju Korea
| | - Hyun-Suk Lee
- Department of Urology; Chonnam National University Medical School; Sexual Medicine Research Center; Chonnam National University; Gwangju Korea
| | - Ho Song Yu
- Department of Urology; Chonnam National University Medical School; Sexual Medicine Research Center; Chonnam National University; Gwangju Korea
| | - Mi Eun Kim
- Department of Biology; BK21-plus Research Team for Bioactive Control Technology; College of Natural Sciences; Chosun University; Gwangju Korea
| | - Jun Sik Lee
- Department of Biology; BK21-plus Research Team for Bioactive Control Technology; College of Natural Sciences; Chosun University; Gwangju Korea
| | - Kwangsung Park
- Department of Urology; Chonnam National University Medical School; Sexual Medicine Research Center; Chonnam National University; Gwangju Korea
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18
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Abstract
Erectile dysfunction (ED) is a common complication of diabetes, affecting up to 75% of all diabetic men. Although the aetiology of diabetic ED is multifactorial, endothelial dysfunction is recognized as a mainstay in the pathophysiology of the disease. Endothelial dysfunction is induced by the detrimental actions of high glucose levels and increased oxidative stress on endothelial cells that make up the vascular lining. Besides directly injuring the endothelium, diabetes might also hamper vascular repair mechanisms of angiogenesis and vasculogenesis. These states exacerbate and maintain endothelial dysfunction, impairing vasorelaxation events and cavernosal blood perfusion, which are crucial for normal erectile function.
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19
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Maiorino MI, Bellastella G, Petrizzo M, Della Volpe E, Orlando R, Giugliano D, Esposito K. Circulating endothelial progenitor cells in type 1 diabetic patients with erectile dysfunction. Endocrine 2015; 49:415-21. [PMID: 25411101 DOI: 10.1007/s12020-014-0478-5] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2014] [Accepted: 11/07/2014] [Indexed: 12/18/2022]
Abstract
Circulating endothelial progenitor cells (EPCs) are bone marrow-derived stem cells able to migrate to sites of damaged endothelium and differentiate into endothelial cells, thereby contributing to vascular repair. Recent studies demonstrated a reduction of EPCs in patients with diabetes mellitus or erectile dysfunction (ED). The aim of this study was to evaluate the circulating levels of different EPCs phenotypes and their relation with testosterone levels in young type 1 diabetic patients with ED. We studied 118 consecutively type 1 diabetic patients and 60 age-matched healthy controls. Erectile function was assessed by completing the International Index of Erectile Function (IIEF-5) and EPCs levels by flow cytometry. Testosterone concentrations were evaluated in all the study population. We identified 38 diabetic patients with ED (Group 1) and 80 patients without ED (Group 2). CD34+KDR+CD133+ cells were significantly lower in patients in Group 1 as compared with those in Group 2 [median and interquartile range, n/10(6) events, 12 (6-16) vs. 18 (13-22), P < 0.001)]. In all participants in the study, there was a significant correlation between circulating CD34+KDR+CD133+ cells and testosterone levels (r = 0.410, P < 0.001), which was highest in Group 1, intermediate in Group 2, and lowest in Group 3 (controls). There was a significant correlation between IIEF-5 score and both CD34+KDR+ (r = 0.459, P = 0.003) and CD34+KDR+CD133+ (r = 0.316, P = 0.050) cells among patients of Group 1, as well as between testosterone levels and most of the EPCs phenotypes. Finally, multivariate regression analysis identified levels of circulating CD34+KDR+ cells as an independent risk factor for ED (β-coefficient 0.348, P = 0.007). In conclusion, type 1 diabetic patients with ED show reduced levels of CD34+KDR+CD133+ cells, whose number correlates with IIEF. Further studies are needed to fully understand the exact mechanisms by which testosterone regulates vascular homeostasis.
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Affiliation(s)
- Maria Ida Maiorino
- Endocrinology and Metabolic Diseases Unit, Department of Medical, Surgical, Neurological, Metabolic Science and Geriatrics, University Hospital at Second University of Naples, Piazza L. Miraglia n° 2, 80138, Naples, Italy,
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20
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Stem cell treatment of erectile dysfunction. Adv Drug Deliv Rev 2015; 82-83:137-44. [PMID: 25446142 DOI: 10.1016/j.addr.2014.11.012] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2014] [Revised: 09/09/2014] [Accepted: 11/08/2014] [Indexed: 12/31/2022]
Abstract
Erectile Dysfunction (ED) is a common disease that typically affects older men. While oral type-5 phosphodieserase inhibitors (PDE5Is) represent a successful first-line therapy, many patients do not respond to this treatment leading researchers to look for alternative treatment modalities. Stem cell (SC) therapy is a promising new frontier for the treatment of those patients and many studies demonstrated its therapeutic effects. In this article, using a Medline database search of all relevant articles, we present a summary of the scientific principles behind SCs and their use for treatment of ED. We discuss specifically the different types of SCs used in ED, the methods of delivery tested, and the methods attempted to enhance SC therapy effect. In addition, we review the current preclinical literature on SC therapy for ED and present a summary of its findings in addition to the single clinical trial published.
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21
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Suzuki E, Nishimatsu H, Homma Y. Stem cell therapy for erectile dysfunction. World J Clin Urol 2014; 3:272-282. [DOI: 10.5410/wjcu.v3.i3.272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2014] [Revised: 05/03/2014] [Accepted: 10/10/2014] [Indexed: 02/06/2023] Open
Abstract
Erectile dysfunction (ED) is an important health problem that has commonly been clinically treated using phosphodiesterase type 5 inhibitors (PDE5Is). However, PDE5Is are less effective when the structure of the cavernous body has been severely injured, and thus regeneration is required. Stem cell therapy has been investigated as a possible means for regenerating the injured cavernous body. Stem cells are classified into embryonic stem cells and adult stem cells (ASCs), and the intracavernous injection of ASCs has been explored as a therapy in animal ED models. Bone marrow-derived mesenchymal stem cells and adipose tissue-derived stem cells are major sources of ASCs used for the treatment of ED, and accumulated evidence now suggests that ASCs are useful in the restoration of erectile function and the regeneration of the cavernous body. However, the mechanisms by which ASCs recover erectile function remain controversial. Some studies indicated that ASCs were differentiated into the vascular endothelial cells, vascular smooth muscle cells, and nerve cells that originally resided in the cavernous body, whereas other studies have suggested that ASCs improved erectile function via the secretion of anti-apoptotic and/or proangiogenic cytokines rather than differentiation into other cell types. In this paper, we reviewed the characteristics of stem cells used for the treatment of ED, and the possible mechanisms by which these cells exert their effects. We also discussed the problems to be solved before implementation in the clinical setting.
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22
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Pelliccione F, D'Angeli A, D'Andrea S, Barbonetti A, Pezzella A, Necozione S, Falone S, Amicarelli F, Francavilla F, Francavilla S. Tadalafil treatment had a modest effect on endothelial cell damage and repair ability markers in men with erectile dysfunction and vascular risk. Asian J Androl 2014; 16:290-4. [PMID: 24407182 PMCID: PMC3955343 DOI: 10.4103/1008-682x.122347] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
The number of the circulating angiogenic cells (CACs) and colony forming units (CFUs) derived from cultured circulating mononuclear cells (MNCs) represents a laboratory surrogate for endothelial cell repair ability. The serum of men with erectile dysfunction (ED) and vascular risk factors (VRFs) showed an increased level of endothelial cell damage/dysfunction markers and reduced the numbers of CACs and CFUs derived from the cells of healthy men. We analyzed whether treating men with ED and VRFs with the selective phosphodiesterase type 5 inhibitor tadalafil improved the endothelial cell repair ability and reduced the levels of the serum markers of endothelial cell damage/dysfunction. MNCs from healthy men were cultured with 20% serum from 36 ED patients to obtain CACs and CFUs. The ED patients were evaluated before and after 4 weeks of treatment with tadalafil (20 mg every other day) or with a placebo. The tadalafil treatment improved erectile function (P = 0.0028), but had no effect on the inhibitory effects of serum from ED patients on the CACs and CFUs derived from healthy men. The levels of endothelin-1 (P = 0.011) and tissue type plasminogen activator (P = 0.005) were reduced after treatment compared to baseline and those of the placebo group, whereas no changes were observed in the E-selectin levels. The tadalafil treatment in the ED patients with VRFs resulted in only a modest effect on the laboratory measures of the endothelial cell damage/dysfunction and repair ability. The proposed beneficial effect of phosphodiesterase type 5 inhibition on vascular homeostasis requires further analysis.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Sandro Francavilla
- Department of Life, Health and Environmental Sciences, Section of Andrology, University of L'Aquila, L'Aquila, Italy
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23
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Suzuki E, Nishimatsu H, Oba S, Takahashi M, Homma Y. Chronic kidney disease and erectile dysfunction. World J Nephrol 2014; 3:220-229. [PMID: 25374815 PMCID: PMC4220354 DOI: 10.5527/wjn.v3.i4.220] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2014] [Revised: 06/22/2014] [Accepted: 09/10/2014] [Indexed: 02/05/2023] Open
Abstract
Erectile dysfunction (ED) is a common condition among male chronic kidney disease (CKD) patients. Its prevalence is estimated to be approximately 80% among these patients. It has been well established that the production of nitric oxide from the cavernous nerve and vascular endothelium and the subsequent production of cyclic GMP are critically important in initiating and maintaining erection. Factors affecting these pathways can induce ED. The etiology of ED in CKD patients is multifactorial. Factors including abnormalities in gonadal-pituitary system, disturbance in autonomic nervous system, endothelial dysfunction, anemia (and erythropoietin deficiency), secondary hyperparathyroidism, drugs, zinc deficiency, and psychological problems are implicated in the occurrence of ED. An improvement of general conditions is the first step of treatment. Sufficient dialysis and adequate nutritional intake are necessary. In addition, control of anemia and secondary hyperparathyroidism is required. Changes of drugs that potentially affect erectile function may be necessary. Further, zinc supplementation may be necessary when zinc deficiency is suspected. Phosphodiesterase type 5 inhibitors (PDE5Is) are commonly used for treating ED in CKD patients, and their efficacy was confirmed by many studies. Testosterone replacement therapy in addition to PDE5Is may be useful, particularly for CKD patients with hypogonadism. Renal transplantation may restore erectile function. ED is an early marker of cardiovascular disease (CVD), which it frequently precedes; therefore, it is crucial to examine the presence of ED in CKD patients not only for the improvement of the quality of life but also for the prevention of CVD attack.
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24
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Identification of endothelial progenitor cells in the corpus cavernosum in rats. BIOMED RESEARCH INTERNATIONAL 2014; 2014:910564. [PMID: 25401106 PMCID: PMC4221983 DOI: 10.1155/2014/910564] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/02/2014] [Revised: 09/17/2014] [Accepted: 09/22/2014] [Indexed: 01/15/2023]
Abstract
The vascular wall resident progenitor cells seem to serve as a local reservoir of cells for vascular repair. It was hypothesized that the corpus cavernosum may contain vascular wall endothelial progenitor cells (EPCs). In this study, we investigated the identification and localization of EPCs in the corpus cavernosum in a rat model. Adult male Sprague-Dawley rats were used to isolate EPCs from corpora cavernosum. To verify the existence and localization of EPCs, EPC-specific markers (CD34, Flk-1, and VE-cadherin) were evaluated by flow cytometric analysis and confocal microscopy. The EPC markers were mainly expressed in the cavernosal sinusoidal endothelial space. EPC-marker-positive cells made up about 3.31% of the corpus cavernosum of normal rat by FACS analysis. As shown by confocal microscopy, CD34+/Flk-1+ and CD34+/VE-cadherin+ positive cells existed in the corpus cavernosum. Our findings imply that regulation of corpus cavernosal EPCs may be a new therapeutic strategy in the treatment of erectile dysfunction.
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25
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Abstract
Stem cell (SC) therapy for erectile dysfunction (ED) has been investigated in 35 published studies, with one being a small-scale clinical trial. Out of these 35 studies, 19 are concerned with cavernous nerve (CN) injury-associated ED while 10 with diabetes mellitus- (DM-) associated ED. Adipose-derived SCs (ADSCs) were employed in 18 studies while bone marrow SCs (BMSCs) in 9. Transplantation of SCs was done mostly by intracavernous (IC) injection, as seen in 25 studies. Allogeneic and xenogeneic transplantations have increasingly been performed but their immune-incompatibility issues were rarely discussed. More recent studies also tend to use combinatory therapies by modifying or supplementing SCs with angiogenic or neurotrophic genes or proteins. All studies reported better erectile function with SC transplantation, and the majority also reported improved muscle, endothelium, and/or nerve in the erectile tissue. However, differentiation or engraftment of transplanted SCs has rarely been observed; thus, paracrine action is generally believed to be responsible for SC’s therapeutic effects. But still, few studies actually investigated and none proved paracrine action as a therapeutic mechanism. Thus, based exclusively on functional outcome data shown in preclinical studies, two clinical trials are currently recruiting patients for treatment with IC injection of ADSC and BMSC, respectively.
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26
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Foresta C, De Toni L, Ferlin A, Di Mambro A. Clinical implication of endothelial progenitor cells. Expert Rev Mol Diagn 2014; 10:89-105. [DOI: 10.1586/erm.09.80] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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27
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Traish AM, Galoosian A. Androgens modulate endothelial function and endothelial progenitor cells in erectile physiology. Korean J Urol 2013; 54:721-31. [PMID: 24255752 PMCID: PMC3830963 DOI: 10.4111/kju.2013.54.11.721] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2013] [Accepted: 09/24/2013] [Indexed: 12/21/2022] Open
Abstract
The incidence of erectile dysfunction (ED) increases with age and cardiovascular disease risk factors, such as hypertension, hyperlipidemia, insulin resistance, obesity, and diabetes. These risk factors are thought to contribute to endothelial dysfunction and atherosclerosis, thus contributing to the pathophysiology of ED. The role of the endothelium in regulating erectile physiology is well established. However, the role of androgens in modulating endothelial function and endothelial repair mechanisms subsequent to vascular injury in erectile tissue remains a subject of intensive research. The clinical and preclinical evidence discussed in this review suggests that androgens regulate endothelial function and also play an important role in the development and maturation of endothelial progenitor cells (EPCs), which are thought to play a critical role in repair of endothelial injury in vascular beds. In this review, we discuss the data available on the effects of androgens on endothelial function and EPCs in the repair of vascular injury. Indeed, more research is needed to fully understand the molecular and cellular basis of androgen action in regulating the development, differentiation, maturation, migration, and homing of EPCs to the site of injury. A better understanding of these processes will be critical to the development of new therapeutic approaches to the treatment of vascular ED.
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Affiliation(s)
- Abdulmaged M Traish
- Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA. ; Department of Urology, Boston University School of Medicine, Boston, MA, USA
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28
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Condorelli RA, Calogero AE, Vicari E, Duca Y, Favilla V, Morgia G, Cimino S, La Vignera S. Endothelial progenitor cells and erectile dysfunction: a brief review on diagnostic significance and summary of our experience. Aging Male 2013; 16:29-32. [PMID: 23597264 DOI: 10.3109/13685538.2013.789159] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The article provides a brief review of the literature concerning the diagnostic use of endothelial progenitor cells in patients with erectile dysfunction. In particular, patients with arterial erectile dysfunction could benefit from the use of this diagnostic marker, which in clinical practice can be used together with more conventional methods such as the penile Doppler. It is very important to acquire diagnostic tools for the diagnosis of sub clinical form of endothelial dysfunction in these patients, in particular when the erectile dysfunction is associated with cardiovascular risk factors.
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Affiliation(s)
- Rosita A Condorelli
- Department of Medical and Pediatric Sciences, University of Catania, Catania, Italy
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29
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Liao CH, Wu YN, Lin FY, Tsai WK, Liu SP, Chiang HS. Testosterone replacement therapy can increase circulating endothelial progenitor cell number in men with late onset hypogonadism. Andrology 2013; 1:563-9. [DOI: 10.1111/j.2047-2927.2013.00086.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2012] [Revised: 02/26/2013] [Accepted: 03/06/2013] [Indexed: 11/29/2022]
Affiliation(s)
| | | | - F.-Y. Lin
- School of Medicine; College of Medicine; Taipei Medical University; Taipei; Taiwan
| | - W.-K. Tsai
- Department of Urology; Mackay Memorial Hospital; Taipei; Taiwan
| | - S.-P. Liu
- Department of Urology; National Taiwan University Hospital; Taipei; Taiwan
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30
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Abstract
Erectile dysfunction is a common clinical entity that affects mainly men older than 40 years. In addition to the classical causes of erectile dysfunction, such as diabetes mellitus and hypertension, several common lifestyle factors, such as obesity, limited or an absence of physical exercise, and lower urinary tract symptoms, have been linked to the development of erectile dysfunction. Substantial steps have been taken in the study of the association between erectile dysfunction and cardiovascular disease. Erectile dysfunction is a strong predictor for coronary artery disease, and cardiovascular assessment of a non-cardiac patient presenting with erectile dysfunction is now recommended. Substantial advances have occurred in the understanding of the pathophysiology of erectile dysfunction that ultimately led to the development of successful oral therapies, namely the phosphodiesterase type 5 inhibitors. However, oral phosphodiesterase type 5 inhibitors have limitations, and present research is thus investigating cutting-edge therapeutic strategies including gene and cell-based technologies with the aim of discovering a cure for erectile dysfunction.
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Affiliation(s)
- Rany Shamloul
- Department of Urology, University of Ottawa, Ottawa, ON, Canada.
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31
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Orabi H, Lin G, Ferretti L, Lin CS, Lue TF. Scaffoldless tissue engineering of stem cell derived cavernous tissue for treatment of erectile function. J Sex Med 2012; 9:1522-1534. [PMID: 22513032 DOI: 10.1111/j.1743-6109.2012.02727.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
INTRODUCTION As one-third of erectile dysfunction (ED) patients do not respond to phosphodiesterase-5 inhibitors, there is great demand for new therapeutic options. Adipose tissue-derived stem cells (ADSCs) represent an ideal source for new ED treatment. AIM To test if ADSCs can be differentiated into smooth muscle cells (SMCs) and endothelial cells (ECs), if these differentiated cells can be used to engineer cavernous tissue, and if this engineered tissue will remain for long time after implantation and integrate into corporal tissue. METHOD Rat ADSCs were isolated and differentiated into SMC and ECs. The differentiated cells were labeled with 5-ethynyl-2-deoxyuridine (EdU) and used to construct cavernous tissue. This engineered tissue was implanted in penises of normal rats. The rats were sacrificed after 1 and 2 months; penis and bone marrow were collected to assess cell survival and inclusion in the penile tissues. MAIN OUTCOME MEASURES The phenotype conversion was checked using morphology, immunocytochemistry (immunohistochemistry [IHC]), and Western blot for SMC and EC markers. The cavernous tissue formation was assessed using rat EC antibody (RECA), calponin, and collagen. The implanted cell survival and incorporation into penis were evaluated with hematoxylin and eosin, Masson's trichrome, and IHC (RECA, calponin, and EdU). RESULTS The phenotype conversion was confirmed with positive staining for SMC and EC markers and Western blot. The formed tissue exhibited architecture comparable to penile cavernous tissue with SMC and ECs and extracellular matrix formation. The implanted cells survived in significant numbers in the penis after 1 and 2 months. They showed proof of SMC and EC differentiation and incorporation into penile tissue. CONCLUSIONS The results showed the ability of ADSCs to differentiate into SMC and ECs and form cavernous tissue. The implanted tissue can survive and integrate into the penile tissues. The cavernous tissue made of ADSCs forms new technology for improvement of in vivo stem cell survival and ED treatment.
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Affiliation(s)
- Hazem Orabi
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
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Pelliccione F, D’Angeli A, Filipponi S, Falone S, Necozione S, Barbonetti A, Francavilla F, Francavilla S. Serum from patients with erectile dysfunction inhibits circulating angiogenic cells from healthy men: relationship with cardiovascular risk, endothelial damage and circulating angiogenic modulators. ACTA ACUST UNITED AC 2012; 35:645-52. [DOI: 10.1111/j.1365-2605.2012.01253.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Qiu XF, Li XX, Chen Y, Lin HC, Yu W, Wang R, Dai YT. Mobilisation of endothelial progenitor cells: one of the possible mechanisms involved in the chronic administration of melatonin preventing erectile dysfunction in diabetic rats. Asian J Androl 2012; 14:481-6. [PMID: 22367180 DOI: 10.1038/aja.2011.161] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Diabetes-induced oxidative stress plays a critical role in the mobilisation of endothelial progenitor cells (EPCs) from the bone marrow to the circulation. This study was designed to explore the effects of chronic melatonin administration on the promotion of the mobilisation of EPCs and on the preservation of erectile function in type I diabetic rats. Melatonin was administered to streptozotocin-induced type I diabetic rats. EPCs levels were determined using flow cytometry. Oxidative stress in the bone marrow was indicated by the levels of superoxide dismutase and malondialdehyde. Erectile function was evaluated by measuring the intracavernous pressure during an electrostimulation of the cavernous nerve. The density of the endothelium and the proportions of smooth muscle and collagen in the corpus cavernosum were determined by immunohistochemistry. The administration of melatonin increased the superoxide dismutase level and decreased the malondialdehyde level in the bone marrow. This effect was accompanied by an increased level of circulating EPCs in the diabetic rats. The intracavernous pressure to mean arterial pressure ratio of the rats in the treatment group was significantly greater, compared with diabetic control rats. The histological analysis demonstrated an increase in the endothelial density of the corpus cavernosum after the administration of melatonin. However, melatonin treatment did not change the proportions of smooth muscle and collagen in the corpus cavernosum of diabetic rats. Chronic administration of melatonin has a beneficial effect on preventing erectile dysfunction (ED) in type I diabetic rats. Promoting the mobilisation of EPCs is one of the possible mechanisms involved in the improvement of ED.
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Affiliation(s)
- Xue-Feng Qiu
- Department of Urology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China
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Zhang H, Albersen M, Jin X, Lin G. Stem cells: novel players in the treatment of erectile dysfunction. Asian J Androl 2012; 14:145-55. [PMID: 22002437 PMCID: PMC3735142 DOI: 10.1038/aja.2011.79] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2011] [Revised: 06/30/2011] [Accepted: 07/19/2011] [Indexed: 01/09/2023] Open
Abstract
Stem cells are defined by their capacity for both self-renewal and directed differentiation; thus, they represent great promise for regenerative medicine. Historically, stem cells have been categorized as either embryonic stem cells (ESCs) or adult stem cells (ASCs). It was previously believed that only ESCs hold the ability to differentiate into any cell type, whereas ASCs have the capacity to give rise only to cells of a given germ layer. More recently, however, numerous studies demonstrated the ability of ASCs to differentiate into cell types beyond their tissue origin. The aim of this review was to summarize contemporary evidence regarding stem cell availability, differentiation, and more specifically, the potential of these cells in the diagnosis and treatment of erectile dysfunction (ED) in both animal models and human research. We performed a search on PubMed for articles related to definition, localisation and circulation of stem cells as well as the application of stem cells in both diagnosis and treatment of ED. Strong evidence supports the concept that stem cell therapy is potentially the next therapeutic approach for ED. To date, a large spectrum of stem cells, including bone marrow mesenchymal stem cells, adipose tissue-derived stem cells and muscle-derived stem cells, have been investigated for neural, vascular, endothelial or smooth muscle regeneration in animal models for ED. In addition, several subtypes of ASCs are localized in the penis, and circulating endogenous stem cells can be employed to predict the outcome of ED and ED-related cardiovascular diseases.
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Affiliation(s)
- Haiyang Zhang
- Minimally Invasive Urology Center, Provincial Hospital Affiliated to Shandong University, Jinan, China
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La Vignera S, Condorelli R, Vicari E, D'Agata R, Calogero AE. Arterial erectile dysfunction: reliability of new markers of endothelial dysfunction. J Endocrinol Invest 2011; 34:e314-20. [PMID: 22234180 DOI: 10.1007/bf03346728] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Blood endothelial progenitor cells (EPC) and microparticles (EMP) have been proposed as markers of endothelial dysfunction. Aim of this study was to evaluate a new immunophenotype of EPC and EMP in patients with arterial erectile dysfunction (AED) compared to psychogenic erectile dysfunction (PED). MATERIALS AND METHODS One hundred patients (63.2±2.6 yr) with AED were enrolled in this study. Their EPC and EMP concentrations were compared to those of 40 patients with PED (64.2±2.7 yr). EPC (CD45(neg)/CD34(pos)/ CD144(pos)) and EMP (CD45(neg)/CD144(pos)/AnnexinV(pos)) blood concentrations were evaluated by flow cytometry. RESULTS Patients with AED had significantly higher blood pressure, triglycerides, homeostasis model assessment index of insulin resistance, and cavernous artery acceleration time and intima-media thickness than PED; whereas international index of erectile function 5 score, HDL-cholesterol, and cavernous artery peak systolic velocity was lower than PED. Both EPC and EMP were significantly higher in patients with AED compared to patients with PED. CONCLUSIONS Patients with AED showed worse metabolic parameters, cavernous artery parameters, and higher EPC and EMP compared to patients with PED. This suggests that AED is an expression of endothelial dysfunction and that EPC and EMP may be considered predictors of endothelial dysfunction in patients with AED.
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Affiliation(s)
- S La Vignera
- Section of Endocrinology, Andrology and Internal Medicine and Master in Andrological, Human Reproduction and Biotechnology Sciences, Department of Internal Medicine and Systemic Diseases, University of Catania, Catania, Italy.
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Castela A, Vendeira P, Costa C. Testosterone, endothelial health, and erectile function. ISRN ENDOCRINOLOGY 2011; 2011:839149. [PMID: 22363891 PMCID: PMC3262643 DOI: 10.5402/2011/839149] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/02/2011] [Accepted: 07/07/2011] [Indexed: 01/02/2023]
Abstract
Experimental and clinical studies have reported that testosterone has a critical role in the maintenance of homeostatic and morphologic corpus cavernosum components, essential for normal erectile physiology. Although the exact mechanisms mediated by testosterone in erectile function are still under investigation, recent research has suggested an important role in the regulation of endothelial cell (EC) biological functions. Besides stimulating the production of EC mediators, testosterone is also thought to promote the vasculogenic reendothelialization process, mediated by bone marrow-derived endothelial progenitor cells. Additionally, testosterone seems to modulate other erectile tissue components, including trabecular smooth muscle cells, nerve fibers, and tunica albuginea structure, all essential for the erectile process. This paper summarizes current data regarding testosterone-induced cellular and molecular mechanisms that regulate penile tissue components, focusing particularly on the role of testosterone in endothelial health and erectile function.
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Affiliation(s)
- Angela Castela
- Institute for Molecular and Cell Biology of the University of Porto (IBMC-UP), Rua do Campo Alegre, 823, 4150-180 Porto, Portugal
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La Vignera S, Condorelli R, Vicari E, D'Agata R, Calogero A. Original immunophenotype of blood endothelial progenitor cells and microparticles in patients with isolated arterial erectile dysfunction and late onset hypogonadism: effects of androgen replacement therapy. Aging Male 2011; 14:183-9. [PMID: 21271942 DOI: 10.3109/13685538.2010.550661] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
OBJECTIVE Blood endothelial progenitor cells (EPCs) and endothelial microparticles (EMPs) have been proposed as markers of endothelial dysfunction. Aim of this study was to evaluate an original immunophenotype of EPCs and EMPs in patients with isolated arterial erectile dysfunction (ED) and late onset hypogonadism (LOH) before and after androgen replacement therapy. MATERIALS AND METHODS Fifty patients (50-64 years) with ED and LOH were selected. EPC (CD45(neg)/CD34(pos)/CD144(pos)) and EMP (CD45(neg)/CD34(neg)/CD144(pos)) blood concentrations were evaluated by flow cytometry. Thirty patients received androgen replacement therapy (Tostrex® ProStrakan) for 6 months (group A), other 20 patients not received androgen therapy for the contraindications in their clinical history (group B). RESULTS After 6 months, group B showed IIEF-5 score, peak systolic velocity and acceleration time significantly worse than group A; in addition EPCs and EMPs were significantly higher in group B compared to group A. CONCLUSIONS Patients with isolated arterial ED and LOH not treated with androgen therapy showed worst vascular parameters measured by penile Doppler and higher EPCs and EMPs compared to treated hypogonadal patients, hence, LOH appears to be an additional vascular risk factor, and these markers may be considered as predictors of cavernous artery disease. Finally, androgen therapy improves endothelial dysfunction.
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MESH Headings
- Age of Onset
- Androgens/administration & dosage
- Antigens, CD/analysis
- Biomarkers
- Blood Flow Velocity/drug effects
- Cell-Derived Microparticles/immunology
- Drug Monitoring
- Endothelium, Vascular/metabolism
- Endothelium, Vascular/physiopathology
- Flow Cytometry
- Hemangioblasts/immunology
- Hormone Replacement Therapy
- Humans
- Hypogonadism/complications
- Hypogonadism/epidemiology
- Hypogonadism/metabolism
- Hypogonadism/physiopathology
- Immunophenotyping/methods
- Impotence, Vasculogenic/drug therapy
- Impotence, Vasculogenic/etiology
- Impotence, Vasculogenic/immunology
- Impotence, Vasculogenic/metabolism
- Impotence, Vasculogenic/physiopathology
- Injections, Subcutaneous
- Male
- Middle Aged
- Risk Factors
- Testosterone/blood
- Treatment Outcome
- Ultrasonography, Doppler, Color
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Affiliation(s)
- Sandro La Vignera
- Section of Endocrinology, Andrology and Internal Medicine, Department of Internal Medicine and Systemic Diseases, University of Catania, Catania, Italy.
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Gou X, He WY, Xiao MZ, Qiu M, Wang M, Deng YZ, Liu CD, Tang ZB, Li J, Chen Y. Transplantation of endothelial progenitor cells transfected with VEGF165 to restore erectile function in diabetic rats. Asian J Androl 2010; 13:332-8. [PMID: 21113173 DOI: 10.1038/aja.2010.116] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
The present study investigated the effect of transplanting endothelial progenitor cells (EPCs) transfected with the vascular endothelial growth factor gene (VEGF165) into the corpora cavernosa of rats with diabetic erectile dysfunction (ED). A rat model of diabetic ED was constructed via intraperitoneal injection of streptozotocin. After streptozotocin treatment, pre-treated EPCs from each of three groups of rats were transplanted into their corpora cavernosa. Our results, following intracavernosal pressure (ICP) monitoring, showed that ICP increased significantly among rats in the trial group when compared to the results from rats in the blank-plasmid and control groups during basal conditions and electrical stimulation (P<0.01 for both comparisons). Histological examination revealed extensive neovascularisation in the corpora cavernosa of rats in the trial group. Fluorescence microscopy indicated that many of the transplanted EPCs in the trial group survived, differentiated into endothelial cells and integrated into the sites of neovascularisation. Based on the results of this study, we conclude that transplantation of VEGF165-transfected EPCs into the corpora cavernosa of rats with diabetic ED restores erectile function.
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Affiliation(s)
- Xin Gou
- Department of Urology, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
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Di Mambro A, Ferlin A, De Toni L, Selice R, Caretta N, Foresta C. Endothelial progenitor cells as a new cardiovascular risk factor in Klinefelter's syndrome. Mol Hum Reprod 2010; 16:411-7. [DOI: 10.1093/molehr/gaq015] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Foresta C, De Toni L, Biagioli A, Ganz F, Magagna S, Caretta N. Increased Levels of Osteocalcin-Positive Endothelial Progenitor Cells in Patients Affected by Erectile Dysfunction and Cavernous Atherosclerosis. J Sex Med 2010; 7:751-7. [DOI: 10.1111/j.1743-6109.2009.01520.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Lombardo F, Tsamatropoulos P, Piroli E, Culasso F, Jannini EA, Dondero F, Lenzi A, Gandini L. Treatment of Erectile Dysfunction Due to C677T Mutation of the MTHFR Gene with Vitamin B6 and Folic acid in Patients Non Responders to PDE5i. J Sex Med 2010; 7:216-23. [DOI: 10.1111/j.1743-6109.2009.01463.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Garolla A, D'Incà R, Checchin D, Biagioli A, De Toni L, Nicoletti V, Scarpa M, Bolzonello E, Sturniolo GC, Foresta C. Reduced endothelial progenitor cell number and function in inflammatory bowel disease: a possible link to the pathogenesis. Am J Gastroenterol 2009; 104:2500-7. [PMID: 19568231 DOI: 10.1038/ajg.2009.332] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Circulating endothelial progenitor cells (EPCs) are essential for endothelial repair and vascular healing. Patients with inflammatory bowel disease (IBD) may suffer from endothelial dysfunction. Reduced EPC number, impaired mobilization, or increased EPC apoptosis may be crucial in this phenomenon. The aim of our study was to investigate the number and function of EPCs in patients with IBD and to assess their endothelial function. METHODS In 100 IBD patients (47 ulcerative colitis (UC) and 53 Crohn's disease (CD)) and 50 healthy controls, EPC number, CXC motif receptor 4 (CXCR4) expression, the percentage of apoptotic circulating EPCs, and the number of colony-forming units were evaluated. Endothelial dysfunction was assessed by luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone levels, and in a subgroup of patients, brachial artery flow-mediated dilation (FMD) was measured. Kruskal-Wallis ANOVA (analysis of variance), Mann-Whitney U two-tailed, and Spearman's rank correlation tests were used to assess differences. RESULTS EPC number was significantly lower in UC patients (39.6 (95% confidence interval (95% CI): 30.7-48.6)) and in CD patients (43.1 (95% CI: 35.9-50.4)) than in healthy controls (97.1 (95% CI: 88.3-105.9)), (P<0.001). LH and FSH levels and CXCR4 expression on EPCs did not significantly differ from controls. Testosterone concentrations and FMD were lower in UC patients. Number of apoptotic EPCs was higher in both UC and CD patients with an impaired ability to generate colony in vitro. CONCLUSIONS We hypothesize that in IBD patients, apoptosis contributes to the reduction of circulating EPC number and to their ability to proliferate in vitro. As this condition represents a risk factor for cardiovascular disease, endothelial function should be evaluated in these patients.
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Affiliation(s)
- Andrea Garolla
- Department of Histology, Microbiology, and Medical Biotechnologies, Center for Male Gamete Cryopreservation, University of Padova, Padova, Italy
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Foresta C, Di Mambro A, Caretta N, De Toni L, Zuccarello D, Ferlin A. Effect of vardenafil on endothelial progenitor cells in hypogonadotrophic hypogonadal patients: role of testosterone treatment. Clin Endocrinol (Oxf) 2009; 71:412-6. [PMID: 19094070 DOI: 10.1111/j.1365-2265.2008.03507.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
CONTEXT Endothelial progenitor cells (EPCs) are bone marrow-derived cells required for endothelial repair. Circulating EPC concentration is low in conditions characterized by endothelial dysfunction but their number can be increased by treatment with phosphodiesterase-5 (PDE5) inhibitors. EPCs are also reduced in hypogonadal men and testosterone (T) treatment restores their concentration. OBJECTIVE To evaluate the relationship between the effect of PDE5 inhibitors and T on EPCs, we analysed the acute effect of vardenafil on the number of EPCs in hypogonadotrophic hypogonadal (HH) patients, before and after T treatment. DESIGN AND SETTING A case-control study at a university andrology centre. PATIENTS Fifteen HH subjects and 25 aged-matched controls. MAIN OUTCOME MEASURES The number of circulating EPCs and progenitor cells (PCs) in HH patients was evaluated after acute vardenafil administration at baseline and after 6 months of T supplementation. RESULTS At baseline, HH men had significantly lower numbers of PCs and EPCs with respect to controls and vardenafil administration had no effect on the number of these cells. After 6 months of T treatment, all HH patients were eugonadal. With respect to baseline, PCs and EPCs were significantly higher and reached the levels observed in controls. Vardenafil administration in HH men at the end of T treatment induced a significant increase in PCs and EPCs in a manner similar to that in controls. CONCLUSIONS This study showed that normal T levels are necessary to restore the responsiveness of EPCs to PDE5 inhibitors, suggesting that T positively modulates PDE5 in bone marrow.
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Affiliation(s)
- Carlo Foresta
- Department of Histology, Microbiology and Medical Biotechnologies, Section of Clinical Pathology and Centre for Male Gamete Cryopreservation, University of Padova, Padova, Italy.
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Abstract
BACKGROUND Erectile dysfunction (ED) is a common sexual problem in men. Under-reporting of ED is widespread, largely because of the embarrassing nature of the condition. AIM This paper reviews the comorbid conditions that are commonly found in patients with ED patients and discusses the implications. DISCUSSION Erectile dysfunction is often associated with other disorders such as diabetes, cardiovascular disease, hypertension, dyslipidaemia, obesity, depression, chronic obstructive pulmonary disease and lower urinary tract symptoms. Although the aetiology of ED is multifactorial, some of the associated comorbid conditions, including diabetes, cardiovascular disease and hypertension, can be a primary cause of ED. Similarly, ED could be a useful marker for comorbid conditions such as cardiovascular disease and diabetes. Effective treatments for ED are available, including the three phosphodiesterase type 5 inhibitors sildenafil citrate, tadalafil and vardenafil HCl. CONCLUSIONS Thorough medical screening of patients with ED is advisable, as this could lead to earlier diagnosis and treatment of comorbid conditions. Conversely, men with conditions such as cardiovascular disease, diabetes, obesity and depression may have undiagnosed ED and should be questioned appropriately to ascertain any erectile problems and initiate appropriate treatment.
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Affiliation(s)
- G Hackett
- Good Hope Hospital, Rectory Road, Sutton Coldfield, UK.
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Esposito K, Ciotola M, Maiorino MI, Giugliano F, Autorino R, De Sio M, Jannini E, Lenzi A, Giugliano D. Circulating CD34+ KDR+ endothelial progenitor cells correlate with erectile function and endothelial function in overweight men. J Sex Med 2009; 6:107-14. [PMID: 19170841 DOI: 10.1111/j.1743-6109.2008.01042.x] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
INTRODUCTION Bone marrow-derived endothelial progenitor cells (EPCs) circulate in the peripheral blood and are involved in endothelial homeostasis and repair. AIM The aim of this study was to assess the circulating levels of different EPC phenotypes in overweight men with or without erectile dysfunction (ED). As endothelial dysfunction is considered a necessary link with ED, endothelium-dependent vasodilation and its relation with EPCs were also investigated. METHODS We studied 30, otherwise healthy, overweight subjects with symptomatic ED for at least 6 months, and 30 age- and weight-matched subjects without ED. Erectile function was assessed by completing the International Index of Erectile Function (IIEF-5), which consists of items 5, 15, 4, 2, and 7 from the full-scale IIEF-15. MAIN OUTCOME MEASURES Seven subpopulations of EPCs were determined by flow cytometry on the basis of the surface expression of CD34, CD133, and KDR antigens: CD34(+), CD133(+), KDR(+), CD34(+)CD133(+), CD34(+)KDR(+), CD133(+)KDR(+), and CD34(+)CD133(+)KDR(+). Endothelium-dependent flow-mediated dilation (FMD) was evaluated in the right brachial artery with a high-resolution ultrasound machine following reactive hyperemia. RESULTS CD34(+)KDR(+) cell count was significantly lower in men with ED as compared with men without ED (63.1 +/- 4 vs. 92.4 +/- 6 cells/10(6) events, mean +/- standard error, P < 0.01). There was a significant direct correlation between circulating CD34(+)KDR(+) cells and the IIEF score (r = 0.44; P = 0.01): men with the severe form of ED presented the lowest level of circulating EPC CD34(+)KDR(+) cells. No significant correlation was found between the circulating levels of the other EPC phenotypes and the IIEF score. There was a significant correlation between CD34(+)KDR(+) cell count and FMD (r = 0.45; P = 0.01), but not between FMD and the other phenotypes. CONCLUSIONS Circulating levels of CD34(+)KDR(+) EPC are reduced in overweight subjects with ED and correlate with the severity of ED. Other EPC phenotypes are not related to ED, suggesting that the CD34(+)KDR(+) phenotype of EPCs may be preferred in future studies.
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Affiliation(s)
- Katherine Esposito
- Department of Geriatrics and Metabolic Diseases, Division of Metabolic Diseases, Second University of Naples, Naples, Italy.
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Abstract
INTRODUCTION The endothelial monolayer plays a crucial role in the vasodilation and hemodynamic events involved in erection physiology. Due to its relevant functions, a close link has been established between endothelial integrity and erectile dysfunction (ED). Endothelial dysfunction is induced by the detrimental actions of vascular risk factors (VRFs), identified as common correlates for the development of cardiovascular disease and ED. It is currently recognized that ED is the early harbinger of a more generalized vascular systemic disorder, and, therefore, an evaluation of endothelial health in ED patients should be of prime relevance. Several noninvasive methods for endothelial function assessment have been proposed, including the Penile Nitric Oxide Release Test (PNORT). AIM To highlight the most recent gathered knowledge on basic and clinical mechanisms underlying loss of cavernosal endothelial function promoted by VRFs and to discuss local and systemic methods for endothelial function assessment in ED individuals, focusing on the PNORT. MAIN OUTCOME MEASURES A complete revision on the novel basic and clinical links between endothelial and ED. METHODS A systematic review of the literature regarding the aforementioned issues. RESULTS Risk factor-associated cavernosal endothelial dysfunction is mostly induced by unifying mechanisms, including oxidative stress and impaired endothelial nitric oxide functional activities, which present clinically as ED. Several techniques to evaluate endothelial dysfunction were revised, with advantages and limitations debated, focusing on our detailed expertise using the PNORT method. CONCLUSIONS The established endothelial-erectile dysfunction connection was thoroughly revised, from basic mechanisms to the clinical importance of endothelial dysfunction assessment as diagnosis for generalized vascular disease. Further studies are required to disclose efficient approaches to repair disabled endothelium and both restore and prevent endothelial dysfunction.
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Affiliation(s)
- Carla Costa
- Faculty of Medicine of the University of Porto, Department of Biochemistry (U38-FCT), Porto, Portugal.
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Is ED Still Only Equal to ED? Eur Urol 2009; 55:794-7; discussion 797-800. [DOI: 10.1016/j.eururo.2008.08.068] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2008] [Accepted: 08/26/2008] [Indexed: 11/23/2022]
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Zeoli A, Dentelli P, Brizzi MF. Endothelial progenitor cells and their potential clinical implication in cardiovascular disorders. J Endocrinol Invest 2009; 32:370-82. [PMID: 19636208 DOI: 10.1007/bf03345729] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Risk factors associated with cardiovascular diseases reduce the availability of endothelial progenitor cells (EPC) by affecting their mobilization and integration into injured vascular sites. The existence of a bone marrow reservoir of EPC has attracted interest, especially as target for therapeutic intervention in different pathological settings. Among the cardiovascular risk factors, hypertension has been shown to be a strongest predictor of EPC migratory impairment. However, at present, data concerning EPC biology are still limited. In this article we provide an overview of data relevant to their potential clinical implications in cardiovascular disorders. In addition, the recent advances in understanding the role of EPC in the pathophysiology of hypertension are discussed.
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Affiliation(s)
- A Zeoli
- Department of Internal Medicine, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy
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50
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Endothelial progenitor cells and cardiovascular homeostasis: Clinical implications. Int J Cardiol 2009; 131:156-67. [DOI: 10.1016/j.ijcard.2008.08.033] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2007] [Revised: 04/02/2008] [Accepted: 08/08/2008] [Indexed: 02/01/2023]
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