内皮祖细胞在勃起功能障碍中的研究进展

近年来,干细胞在阴茎海绵体血管内皮细胞修复中的作用已成为研究的热点.内皮祖细胞(Endothelial progenitor cells,EPCs)作为内皮细胞的前体细胞,是一种成体干细胞,可通过直接分化成内皮细胞及自/旁分泌方式修复受损的内皮组织.EPCs经基因修饰后,有望成为一种治疗勃起功能障碍(Erectile Dysfunction,ED)的新方法.     

脂肪源性干细胞治疗阴茎勃起功能障碍的研究进展

脂肪源性干细胞(ADSCs)是从脂肪组织中分离得到的一种多能干细胞,具有自我更新和多向分化潜能,可向神经细胞、平滑肌细胞及内皮细胞等多种细胞类型分化。而勃起功能障碍(ED)是一种常见的男性性功能障碍疾病,对患者及其伴侣的生活造成了很大的负面影响。目前治疗ED的方法有手术及药物等,其中5-磷酸二酯酶抑制剂作为临床治疗ED的一线用药,仍对少部分患者不敏感,而且存在无法改善或者治愈ED的病理基础。迄今为止的动物试验及临床前期研究已经证实了ADSCs治疗ED的安全性及有效性,其可通过旁分泌作用达到治疗ED的作用。本文就近5年来ADSCs治疗ED的研究进展进行综述。     

VEGF与颅脑损伤修复机制的研究进展

干细胞对颅脑损伤的治疗是当前研究的热点.但干细胞移植仍然存在排斥、存活率低等很多问题.研究招募自体骨髓间充质干细胞至损伤部位,并诱导定向分化为神经元细胞达到修复损伤的作用,从而成为颅脑损伤治疗方法的又一大热点.血管内皮细胞生长因子及其受体广泛分布于中枢神经系统,血管内皮细胞生长因子可促进脑微循环重塑、诱导骨髓间充质干细胞向血管内皮分化,可抑制神经元死亡和凋亡,并且具有招募、诱导自体神经祖细胞及骨髓间充质干细胞定向分化为神经元的功能.血管内皮细胞生长因子、骨髓间充质干细胞与神经营养因子之间形成网络机制,共同促进颅脑损伤修复.这种自身修复治疗有望成为一种有良好前景的研究方案.     

干细胞治疗阴茎勃起功能障碍的研究进展

阴茎勃起功能障碍(ED)是指男性反复或者持续性的难以达到和维持充分的阴茎勃起,无法完成性交或满意性活动的病理现象。海绵体神经(CN)损伤引起的勃起神经反射中断,是患者出现ED的直接原因,此外,CN损伤后,阴茎海绵体组织平滑肌细胞和内皮细胞凋亡增加,海绵体平滑肌纤维数量减少加重了ED的发生。因此,尽早干预CN损伤的病理过程,促进CN再生是治疗CN损伤性ED的关键。近年来,干细胞在ED治疗中的应用日益成为临床研究热点。现对胚胎干细胞(ESC)、间充质干细胞(MSCs)、肌源性干细胞(MDSCs)、脂肪干细胞(ADSCs)在ED治疗中的研究综述如下。     

高血压与勃起功能障碍相互关系研究进展

勃起功能障碍(ED)与高血压之间的关系是男科学研究的重点领域。目前研究认为,这两种疾病拥有相似的病理生理过程,如氧化应激效应造成血管内皮损害以及RhoA/Rho激酶活性上调。两种疾病均为血管功能损害这一病理过程的不同阶段。定期细致而全面评估高血压合并ED患者病情,并予以合理药物治疗显得尤为重要。在高血压患者中,5型磷酸二酯酶抑制剂无论是单用还是联合抗高血压药物使用都取得了令人满意的效果。目前,基因治疗以及脂肪源性干细胞治疗都展现出了良好的前景,通过转化医学方法可使其更好的为临床服务。     

尿源性干细胞在泌尿系统疾病应用中的研究进展

尿源性干细胞(USCs)是从尿液中分离、提取出的间充质干细胞, 具有多向分化能力和无限增殖潜能。USCs较其他间充质干细胞的提取更为简单、无创。目前已有研究表明USCs可用于间质性膀胱炎、尿失禁以及糖尿病膀胱等泌尿系统疾病的治疗。研究表明USCs可结合组织工程技术用于输尿管缺损重建、膀胱重建以及尿道的修复。此外, 也有部分研究将USCs作为诱导多能干细胞的细胞来源, 进行泌尿系统疾病的研究以及治疗。     

神经干细胞移植对大鼠脊髓损伤后BDNF与GAP-43基因表达的影响

目的：研究海马源性神经干细胞(NSCs)移植对大鼠脊髓损伤(SCI)后生长相关蛋白43(GAP-43)及脑源性神经营养因子(BDNF)基因表达的影响，探讨神经干细胞移植修复大鼠脊髓损伤的机制。方法：NSCs提取自新生胎鼠的海马区，经过培养及鉴定。实验分为3组：NSCs移植组、DMEM填充组、正常对照组。大鼠SCI后第7d移植NSCs，应用RT-PCR法观察NSCs移植后，大鼠脊髓损伤区GAP-43和BDNF基因表达的变化。结果：NSCs移植组较单纯损伤组明显增强了GAP-43mRNA与BDNFmRNA的表达。结论：NSCs移植后改变脊髓损伤区的微环境，上调BDNFmRNA，促进GAP-43mRNA的表达，是修复脊髓损伤的机制之一。     

细胞因子治疗勃起功能障碍的研究进展

细胞因子与勃起功能障碍(ED)密切相关。研究发现,4类相关细胞因子和ED发生与治疗有关。促进血管再生的细胞因子可以改善血管内皮功能,促进内皮再生从而改善勃起功能;促进神经再生的细胞因子通过保护海绵体神经改善勃起功能;保护平滑肌功能的细胞因子通过促进平滑肌表达,抑制阴茎纤维化改善勃起功能;炎症相关的细胞因子通过作用于平滑肌上相应受体松弛平滑肌改善勃起功能。与5型磷酸二酯酶(PDE-5)抑制剂相比,细胞因子治疗ED更有针对性。但是,目前的实验模型大多数为大鼠且缺乏大样本的研究,限制了细胞因子进一步应用于临床。所以,虽然血管内皮生长因子(VEGF)、胰岛素样生长因子1(IGF-1)、脑源性神经营养因子(BDNF)、神经生长因子(NGF)等可以显著改善ED动物的勃起功能,但是需要大型动物实验和大样本的实验进一步证实其治疗效果和安全性。     

血管内皮生长因子的神经保护作用

血管内皮生长因子（vascular endothelial growth factor,VEGF）由Ferrara等在牛垂体滤泡星状细胞体外培养液中首先纯化出来,又称血管通透因子（vascular permeability factor,VPF）。它是一种内皮细胞特异的有丝分裂原,通过与其受体结合而发挥促进内皮细胞增殖、加速新生血管形成、提高血管通透性等生物学特性。最近研究表明,血管内皮因子有类似于血管源性的神经保护和神经营养作用。     

神经干细胞移植对大鼠脊髓损伤后BDNF与GAP-43基因表达的影响

目的:研究海马源性神经干细胞(NSCs)移植对大鼠脊髓损伤(SCI)后生长相关蛋白43(GAP-43)及脑源性神经营养因子(BDNF)基因表达的影响,探讨神经干细胞移植修复大鼠脊髓损伤的机制.方法:NSCs提取自新生胎鼠的海马区,经过培养及鉴定.实验分为3组:NSCs移植组、DMEM填充组、正常对照组.大鼠SCI后第7d移植NSCs,应用RTPCR法观察NSCs移植后,大鼠脊髓损伤区GAP-43和BDNF基因表达的变化.结果:NSCs移植组较单纯损伤组明显增强了GAP-43mRNA与BDNFmRNA的表达.结论:NSCs移植后改变脊髓损伤区的微环境,上调BDNFmRNA,促进GAP-43mRNA的表达,是修复脊髓损伤的机制之一.     

Endothelium-specific gene and stem cell-based therapy for erectile dysfunction

Erectile dysfunction （ED） commonly results from endothelial dysfunction of the systemic vasculature. Although phosphodiesterase type 5 （PDE-5） inhibitors are effective at treating most cases of ED, they must be taken routinely and are ineffectual for a meaningful number of men. In recent years gene and stem cell-based therapies targeted at the penile endothelium have been gaining momentum in preclinical studies. These early studies reveal that gene and stem cell-based therapies may be both enduring and efficacious, and may eventually lead to a cure for ED. The following review will highlight our current understanding of endothelial-specific gene and stem cell-based therapies performed to date in a number of experimental animal models.     

Gene and stem cell therapy for erectile dysfunction

Erectile dysfunction (ED) is defined as the inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance. ED is a highly prevalent health problem with considerable impact on the quality of life of men and their partners. Although the treatment of ED with oral phosphodiesterase type V (PDE5) inhibitors is effective in a wide range of individuals, it is not efficacious in all patients. The failure of PDE5 inhibitors happens mainly in men with diabetes, non-nerve sparing radical prostatectomy, and high disease severity. Therefore, improved therapies based on a better understanding of the fundamental issues in erectile physiology and pathophysiology have recently been proposed. Here, we summarize studies on ED treatment using gene and stem cell therapies. Adenoviral-mediated intracavernosal transfer of therapeutic genes, such as endothelial nitric oxide synthase (eNOS), calcitonin gene-related peptide (CGRP), superoxide dismutase (SOD), and RhoA/Rho kinase and mesenchymal stem cell-based cell and gene therapy strategy for the treatment of age- and diabetes-related ED are the focus of this review.     

Stem cells: novel players in the treatment of erectile dysfunction

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.     

Stem and endothelial progenitor cells in erection biology

Erectile dysfunction (ED) is defined as the consistent inability to obtain or maintain an erection for satisfactory sexual relations. The past 20 years of basic science research on erection physiology has been devoted to investigating the pathogenesis of ED and has led to the conclusion that ED is predominately a disease of vascular origin with dramatic changes occurring in the endothelium. Research has also led to an understanding of the biochemical factors and intracellular mechanisms responsible for corporal smooth muscle contraction and relaxation and the influence of endothelium-derived relaxing factors. The development of methods to deliver both stem and endothelial cells to the penis has kindled a keen interest in treating ED with gene- and cell-based therapies. In this paper, erection physiology and stem cell biology is reviewed, and the potential application of novel cell-based therapies for the treatment of ED is discussed.     

脂肪来源干细胞在下尿路修复重建中的应用

脂肪来源干细胞具有自我更新及多向分化潜能,能够分化成平滑肌细胞、尿路上皮样细胞、内皮细胞、神经样细胞等,并且可以分泌多种生长因子。因此,脂肪来源干细胞结合组织工程技术,已成为近年来下尿路修复重建实验研究的热点之一。本文就利用脂肪来源干细胞作为种子细胞,对膀胱缺损、压力性尿失禁、勃起功能障碍等疾病的组织工程修复进行综述。     

Stem Cell Therapy in Cartilage Repair—Culture-Free and Cell Culture–Based Methods

In order to overcome potential problems associated with autologous chondrocyte implantation, mesenchymal stem cell-based therapies could be potential alternatives. Conventional stem cell-based therapy accompanies the separation of cells from tissue followed by monolayer culture for the expansion of cell numbers. On the other hand, the cost of cell culture under quality control is high, which could be a potential barrier for industrialization. In order to reduce the cost associated cell culture, culture-free cell-based therapies have been investigated with the use of bone marrow aspirate. In this chapter, we will introduce the three stem cell-based therapies in cartilage repair. The first two procedures are using cell culture methods and the last one with cell-free method. All the three methods have been into the stage of clinical trials and their surgical procedures as well as their preliminary results will be reported.     

【原创论文】他达拉非治疗有血管风险的ED男性对改善内皮细胞损伤和修复效果不明显

循环成血管细胞数（CACs）与来源于循环单核细胞的集落形成单位数（CFUs）在实验室检测中代表内皮细胞的修复能力。具有血管危险因素（VRF）的ED男性血清中内皮细胞损伤／功能障碍的标志物水平增加以及来源于健康男性的循环成血管细胞数和集落形成单位数减少。我们研究了选择性磷酸二酯酶5抑制剂他达拉非能否改善有VRF的ED男性内皮细胞的修复能力以及减少血清内皮细胞损伤／功能障碍标志物的水平。36例ED患者的20％血清培养健康男性的单核细胞以检测循环成血管细胞和集落形成单位。检测JED患者服用他达拉非（隔日20毫克）及安慰剂前及用药4周后的血清标志物。他达拉非治疗能改善勃起功能（P=0．0028）,但不能减轻ED患者的血清对健康男性的CACs和CFUs的抑制。与基线及安慰剂比较,治疗后内皮素．1的水平（P=0．011）和组织型纤溶酶原激活物（P=0．005）均减少,而E-选择素水平无变化。有血管危险因素的ED患者经他达拉非治疗后实验室检测内皮细胞损伤与修复能力显示只有轻微影响。PDE5抑制剂对血管稳态的可能益处尚需进一步研究。     

高同型半胱氨酸血症与勃起功能障碍研究进展

高同型半胱氨酸血症(hyperhomocysteinemia,HHcy)是心血管疾病的一个重要危险因素之一。流行病学研究表明勃起功能障碍(ED)与心血管疾病的发生密切相关。HHcy可能是ED的一个新的独立危险因素,HHcy导致ED的机制尚不十分清楚,可能与血管内皮细胞损伤、活性氧(ROS)、动脉粥样硬化等有关。HHcy与ED的关系仍需进一步研究,检测血浆Hcy和叶酸水平以及亚甲基四氢叶酸还原酶(MTHFR)基因型有助于ED诊断,尤其是对于年轻患者以及有心血管病家族史患者。对于HHcy伴ED患者的治疗,可先通过单独服用叶酸或结合维生素B6和维生素12来降低Hcy水平,然后进行5型磷酸二酯酶抑制剂(PDE5i)的治疗。本文就HHcy与ED的研究进展作一综述。