电针与干细胞移植治疗脊髓损伤的研究进展

电针与干细胞移植联合修复脊髓损伤(SCI)是一种极具前景的治疗方法。从单一电针或干细胞移植发展到干细胞联合多种干预因素作用,以此促进受损神经功能的修复。本文就当前脊髓损伤病理表现及生物学标记、电针与干细胞移植及其联合治疗加以综述,并对SCI的治疗前景与存在问题进行展望。     

骨髓干细胞归巢研究进展

干细胞已越来越多应用于各种组织器官损伤的再生治疗，包括缺血性心脏病的治疗。干细胞修复作用的前提是细胞归巢，即心肌梗死等细胞损伤坏死引起一系列信号分子的释放，内源性骨髓干细胞或移植的外源性干细胞定向趋化迁移至损伤处，发挥修复作用。心肌内局部注射的干细胞产生的移行也是一种归巢。深入理解干细胞的归巢过程和机制对提高移植效果意义重大。     

多能干细胞在肝脏损伤和修复过程中的免疫调节作用

免疫平衡被打破是肝脏发生损伤或纤维化的基础。因此针对肝脏疾病的治疗不仅需要依赖再生医学发挥肝脏的替代功能,还需要依赖于免疫调节手段。肝脏损伤修复的免疫学基础、多能干细胞用于异体移植的免疫学基础,以及干细胞在治疗肝脏疾病中的免疫调节作用的研究进展发现,多能干细胞尤其是间充质干细胞不仅具有低免疫原性和免疫抑制作用,具备了异体移植的免疫学基础,还可通过免疫调节作用,改善肝脏的局部免疫微环境,从而改善免疫反应导致的肝损伤。提示,多能干细胞用于肝脏疾病的治疗不仅可以满足肝脏替代功能的需求,还可以满足免疫调节能力的需求。多能干细胞移植将成为理想的肝脏疾病治疗手段。     

干细胞与胃肠道黏膜的自我更新和损伤修复

干细胞是一类具有自我更新和多向分化潜能的细胞。近期研究发现干细胞在胃肠道黏膜自我更新和损伤修复中发挥重要作用，其可使胃肠道黏膜处于动态平衡状态，并维持胃肠道黏膜的完整性。目前干细胞作用于胃肠道黏膜的功能和机制尚未完全明了。随着对干细胞研究的不断深入，干细胞应用将为胃肠疾病提供新的治疗手段。本文就干细胞在胃肠道黏膜自我更新和损伤修复中的作用和机制作一综述。     

干细胞在心肌梗死治疗中的研究进展

细胞移植治疗的出现为众多心衰患者带来了新的希望,干细胞是主要的细胞来源。胚胎干细胞能分化为真正的心肌细胞,是心肌修复治疗中一种理想的细胞来源,但其受免疫和伦理学方面的限制；成体干细胞作为自体细胞移植治疗对研究者来说则具有很大的吸引力,但其分化潜能则不如胚胎干细胞。目前,用于基础研究和临床试验的成体干细胞主要来源于骨髓,且认为只有骨髓间充质干细胞能分化为心肌细胞。本文主要讨论了不同于细胞移植在受损心肌修复治疗中的作用。     

骨髓间充质干细胞治疗胰腺疾病研究现状与前景

胰腺疾病的发病率逐年增加,目前针对胰腺疾病治疗以控制临床症状为主,但胰腺细胞损伤修复及功能恢复研究进展缓慢.目前干细胞因其多向分化增殖和对损伤与疾病导致的细胞损伤有修复功能,近年在疾病治疗方面应用广泛.已有大量实验证实,胰腺干细胞在移植后能分化胰腺功能细胞,在胰腺内外分泌功能恢复及胰腺细胞损伤修复中扮演重要作用.尤其是骨髓间充质干细胞,在治疗胰腺疾病方面的体内外研究成果显著,为干细胞治疗应用于胰腺疾病的临床治疗奠定了理论和实践基础.本文概述该细胞在急慢性胰腺炎及胰腺癌的研究进展及不足,证实了干细胞有望成为治疗胰腺疾病新方法之一.     

兔骨髓间充质干细胞诱导分化为血管内皮细胞的实验研究

干细胞移植治疗是当今一种极为先进的医疗技术,该治疗方法对于临床中某些疑难杂症的医治带来了希望的曙光,而干细胞移植有着让人体组织细胞修复、重建的作用。MSCs在人体中属于骨髓间充质干细胞,其可以对骨髓中的造血干细胞有促进、支持等作用[1]。近年来,干细胞移植治疗在临床组织再生各方面应用广泛,但是干细胞是具有多向分化潜能的细胞,移植后有成瘤的风险,其安全性需进一步研究[2,3]。     

缺血性心脏病干细胞治疗进展

干细胞移植使缺血再灌注中损伤心肌的再生和修复成为可能。研究表明,移植的干细胞活性低且不能存留于心肌组织,所以再生心肌能力有限。优化干细胞移植的各环节成为缺血性心脏病受损心肌干细胞治疗的关键。该文从干细胞来源、体外诱导方法、干细胞预处理、移植方式、移植时机及移植后的监测等方面对心肌干细胞治疗进展作一介绍。     

成体干细胞与肺损伤修复

尽管肺有较强的代偿能力,但如何促进肺的修复再生是提高终末肺疾病患者肺功能的关键之一。近年来应用干细胞治疗提供了我们修复组织损伤的新途径,本文就成体肺内源性干细胞和骨髓源性干细胞的生物学特性、分离培养方法及其在肺损伤中的修复作用作一综述。     

骨髓间充质干细胞治疗缺血性脑血管病研究进展

骨髓间充质干细胞是存在于骨髓中的一种具有跨胚层分化潜能的干细胞。近年来研究发现其可在中枢神经系统内存活并能分化为神经样细胞，在体外也可通过诱导向神经细胞转化，并对脑缺血、脑外伤等疾病的神经功能的缺损有改善作用。其取材方便、体外扩增迅速且能以多种途径移植包括静脉移植、脑内移植。故骨髓间充质干细胞在中枢神经系统损伤修复中的临床应用前景广阔。     

Origins of Metaplasia in Barrett’s Esophagus: Is this an Esophageal Stem or Progenitor Cell Disease?

The incidence of esophageal adenocarcinoma has been increasing in Western countries over the past several decades. Though Barrett’s esophagus, in which the normal esophageal squamous epithelium is replaced with metaplastic intestinalized columnar cells due to chronic damage from gastroesophageal reflux, is accepted as the requisite precursor lesion for esophageal adenocarcinoma, the Barrett’s esophagus cell of origin and the molecular mechanism underlying esophageal epithelial metaplasia remain controversial. Much effort has been dedicated towards identifying the Barrett’s esophagus cell of origin since this could lead to more effective prevention and treatment strategies for both Barrett’s esophagus and esophageal adenocarcinoma. Previously, it was hypothesized that terminally differentiated esophageal squamous cells might undergo direct conversion into specialized intestinal columnar cells via the process of transdifferentiation. However, there is increasing evidence that stem and/or progenitor cells are molecularly reprogrammed through the process of transcommitment to differentiate into the columnar cell lineages that characterize Barrett’s esophagus. Given that Barrett’s esophagus originates at the gastroesophageal junction, the boundary between the distal esophagus and gastric cardia, potential sources of these stem and/or progenitor cells include columnar cells from the squamocolumnar junction or neighboring gastric cardia, native esophageal squamous cells, native esophageal cuboidal or columnar cells from submucosal glands or ducts, or circulating bone marrow-derived cells. In this review, we focus on native esophageal specific stem and/or progenitor cells and detail molecular mediators of transcommitment based on recent insights gained from novel mouse models and clinical observations from patients.     

Origins of Metaplasia in the Esophagus: Is This a GE Junction Stem Cell Disease?

The incidence of esophageal adenocarcinoma (EAC) and its precursor lesion Barrett’s esophagus (BE) has been increasing steadily in the western world in recent decades. Understanding the cellular origins of BE and the conditions responsible for their malignant transformation would greatly facilitate risk assessment and identification of patients at risk of progression, but this topic remains a source of debate. Here, we review recent findings that have provided support for the gastroesophageal junction (GEJ) as the main source of stem cells that give rise to BE and EAC. These include both gastric cardia cells and transitional basal cells. Furthermore, we discuss the role of chronic injury and inflammation in a tumor microenvironment as a major factor in promoting stem cell expansion and proliferation as well as transformation of the GEJ-derived stem cells and progression to EAC. We conclude that there exists a large amount of empirical support for the GEJ as the likely source of BE stem cells. While BE seems to resemble a successful adaptation to esophageal damage, carcinogenesis appears as a consequence of natural selection at the level of GEJ stem cells, and later glands, that expand into the esophagus wherein the local ecology creates the selective landscape for cancer progression.     

Real-time monitoring of luminal esophageal temperature during left atrial radiofrequency catheter ablation for atrial fibrillation: observations about esophageal heating during ablation at the pulmonary vein ostia and posterior left atrium

INTRODUCTION: Left atrial radiofrequency catheter ablation (RFA) is gaining acceptance as treatment for drug-refractory atrial fibrillation (AF). This therapy has been associated with esophageal injury and atrioesophageal fistula formation causing death. METHODS: We describe 3 patients undergoing catheter ablation for AF during real-time monitoring of luminal esophageal temperature. RESULTS: We observed heating of the esophagus during short duration low power RFA, at either the left or right pulmonary vein ostia. Cryoablation at the pulmonary vein ostium in one patient resulted in esophageal cooling. Furthermore, we observed that fluoroscopic localization of the ablation catheter at a site apparently distant from the esophagus is not adequate to assure avoidance of ablation-induced esophageal heating. CONCLUSIONS: Real-time monitoring of luminal esophageal position and temperature is feasible, enhances recognition of esophageal heating, and may add useful information beyond that provided by fluoroscopic assessment of esophageal position. There is a potential role for esophageal monitoring to help avoid thermal injury to the esophagus during catheter ablation for atrial fibrillation.     

Atrioesophageal Fistula in the Era of Atrial Fibrillation Ablation: A Review

The purpose of this review is to understand the epidemiology, clinical features, etiopathogenesis, and management of atrioesophageal fistula (AEF) after atrial fibrillation (AF) ablation. The incidence of AEF after AF ablation is 0.015%-0.04%. The principal clinical features include fever, dysphagia, upper gastrointestinal bleeding, sepsis, and embolic strokes. The close proximity of the esophagus to the posterior left atrial wall is responsible for esophageal injury during ablation. Prophylactic proton pump inhibitors, esophageal temperature monitoring, visualization of the esophagus during catheter ablation, esophageal protection devices, and avoidance of energy delivery in close proximity to the esophagus play an important role in preventing esophageal injury. Early surgical repair or esophageal stenting are the mainstay of treatment. Eliminating esophageal injury during AF ablation is of utmost importance in preventing AEF. A high index of suspicion and early intervention is necessary to prevent fatal outcomes.     

How to Make a Barrett Esophagus: Pathophysiology of Columnar Metaplasia of the Esophagus

Barrett esophagus is defined as a specialized intestinal replacing the squamous epithelium of the esophageal mucosa in response to gastroesophageal reflux. Barrett metaplasia is a healing process that develops to protect the esophagus from further damage. Although mechanisms by which Barrett metaplasia evolves toward dysplasia and adenocarcinoma have been extensively studied, the process by which squamous epithelium is replaced by specialized intestinal metaplasia is poorly understood. Barrett esophagus develops when defense mechanisms in the esophageal mucosa (luminal secretion of mucus, bicarbonate, growth factors, etc.) are overwhelmed by an ongoing cycle of mucosal injury and repair. Hydrogen ion, pepsin, trypsin, and bile acids are considered harmful agents that synergistically invade the esophageal mucosa. Areas of destroyed squamous epithelium are then progressively reepithelized by a columnar epithelium that may originate from multipotent stem cells located within the basal layer of the normal esophageal mucosa or in the ducts of submucosal glands.     

Expression of the putative stem cell marker Musashi‐1 in Barrett's esophagus and esophageal adenocarcinoma

The cancer stem cell theory states that cancers contain tumor‐forming cells that have the ability to self‐renew as well as give rise to cells that differentiate. Cancer stem cells have been identified in several solid tumors, but stem cells in normal human esophagus or in Barrett's esophagus or adenocarcinoma have not been reported. Musashi‐1 is expressed by the crypt base columnar cells identified as intestinal stem cells. In other diseases of the gastrointestinal tract, local inflammation of the tunica mucosa may be an initiating factor of alteration of focal tissue ‘niches,’ where dormant stem cells locate. The present study investigated whether Musashi‐1 is expressed in the esophagus and its relation to immune inflammation of the mucosa in Barrett's esophagus and esophageal adenocarcinoma. A total of 41 esophageal tissue specimens from 41 patients were studied. Of these, 15 were esophageal adenocarcinoma, 17 were Barrett's esophagus (10 intestinal metaplasia and 7 dysplasia), and 9 were normal squamous esophagus tissue specimens from patients without esophageal pathology. Immunohistochemistry was performed using antibodies to Musashi‐1 and to a set of cell type‐specific markers. A multiplexed tandem polymerase chain reaction method was used to measure the relative mRNA expression levels of Musashi‐1 and the specific dendritic cell marker dendritic cell‐specific intercellular molecule‐3 (ICAM‐3)‐grabbing nonintegrin. Immunohistochemistry demonstrated the presence of small numbers of Musashi‐1+ cells scattered in the connective tissue stroma and within the epithelium in cardiac‐type glands in biopsies from patients without Barrett's esophagus. Musashi‐1 expression was present in Barrett's intestinal metaplasia and in dysplastic Barrett's in which the majority of epithelial cells in individual glands expressed this antigen. Expression of Musashi‐1 was highest in esophageal adenocarcinoma, where it was most intense in glands that displayed features of early stages of adenocarcinoma formation. In contrast, Musashi‐1 staining level was weaker in glands that displayed features of advanced adenocarcinoma. Double immunostaining with proliferating cell nuclear antigen showed low proliferation in the vast majority of Musashi‐1+ cells. Musashi‐1 mRNA expression levels were significantly higher in esophageal adenocarcinoma than in normal esophagus or Barrett's esophagus tissues. Dendritic cell‐specific intercellular molecule‐3 (ICAM‐3)‐grabbing nonintegrin (DC‐SIGN) mRNA expression levels were significantly increased in both Barrett's tissues and adenocarcinoma tissues. Expression of the putative stem cell marker Musashi‐1 is absent in normal squamous epithelium, weak in esophageal cardiac‐type glands and Barrett's esophagus, and markedly increased in adenocarcinoma, especially in glands displaying features of early cancer development. Musashi‐1 expressing cells may be significant in the etiology of Barrett's esophagus and adenocarcinoma, and perhaps even a cell of origin for this disease. We speculate that immune inflammation occurring in Barrett's esophagus alters the mucosal microenvironment in a manner which is favorable to the activation of dormant stem cells.     

Role of endoscopy in caustic injury of the esophagus

Caustic injury of the esophagus is a problematic condition challenging endoscopists worldwide. Althoughthe caustic agents and motives are different among countries and age groups, endoscopy still plays an invaluable role in diagnosis and treatment. Endoscopy can determine the severity of caustic ingestion which is of great importance in choosing appropriate treatment. However, some aspects of endoscopy in diagnosis of caustic injury remain controversial. Whether or not all patients need endoscopy, when to perform endoscopy and how to assess the severity are just some examples of these controversies. Due to lack of randomized controlled trials, many findings and suggestions are inconclusive. Computerized tomography scan of the chest and abdomen gains popularity in assessing the severity of caustic injury and avoiding unnecessary surgery. If esophageal stricture eventually develops, endoscopic dilatation is a mainstay. Maneuvers such as steroid injection and esophageal stent may be used in a refractory stricture. Nevertheless, some patients have to undergo surgery in spite of vigorous attempts with esophageal dilatation. To date, caustic injury remains a difficult situation. This article reviews all aspects of caustic injury of the esophagus focusing on endoscopic role. Pre-endoscopic management, endoscopy and its technique in acute and late phase of caustic injury including the endoscopic management of refractory stricture, and the treatment outcomes following each endoscopic intervention are thoroughly discussed. Finally, the role of endoscopy in the long term follow-up of patients with esophageal caustic injury is addressed.     

莪术油对小鼠糜烂性食管炎的治疗作用

背景:莪术油具有抗菌、抗炎、促进黏膜修复再生等作用,临床上广泛应用于宫颈糜烂的治疗。目的:建立小鼠急性糜烂性食管炎(EE)模型,比较莪术油与常用黏膜保护剂磷酸铝、蒙脱石对EE的治疗作用。方法:100只健康雄性昆明小鼠随机分为正常对照组、模型组、磷酸铝组、蒙脱石组和莪术油组。模型组和三组治疗组以食管灌注稀盐酸造模,三组治疗组造模后分别予食管灌注相应药物14 d。处死小鼠,观察食管黏膜大体和组织病理学表现。结果:模型组小鼠食管黏膜鳞状上皮增生,黏膜糜烂明显,大量炎性细胞浸润,大体和组织学评分显著高于正常对照组(P0.05)。三组治疗组食管黏膜损伤均较模型组显著减轻(P0.05),以莪术油组为著,该组黏膜愈合良好,大体和组织学评分显著低于磷酸铝组和蒙脱石组(P0.05),与正常对照组相比差异无统计学意义(P0.05)。结论:莪术油对小鼠急性EE模型有明显治疗作用,效果优于常用黏膜保护剂,为临床研发特异性食管黏膜保护剂提供了实验依据。