内皮祖细胞在血管组织工程研究中的应用现状

组织工程血管是修复紫绀型先心病右心室流出道的潜在替代材料,实验研究表明外周血内皮祖细胞(endothelial progenitor cell,EPC)可作为构建组织工程血管的良好种子细胞。现阶段国内外对组织工程血管的研究方兴未艾,EPC在血管组织工程研究中的应用还处在体外培养或动物实验阶段,尚无临床应用报道。近来某些基础研究的成果对于新生血管的形成和EPC的自动募集机制有了合理的解释,其中缺氧被认为是重要的始动因素,这些研究成果也为EPC作为种子细胞应用于血管组织工程提供了理论基础。所以,阐明EPC的低氧诱导机制及其在血管组织工程的应用必将有助于复杂紫绀型先心病的外科治疗。本文主要介绍了目前该领域研究现状及相关研究基础的进展,并总结提出了在EPC研究和未来临床应用中需解决的问题。     

组织工程产品的种类及应用——组织工程连载之六

组织工程产品包括人造皮肤、血管、软骨、骨、角膜、心脏瓣膜、气管、肌腱、韧带、神经、肌肉、骨髓、生殖道、尿道、肠、乳房、肝脏、肾脏、胰脏、心脏、膀胱、手等,但绝大部分处于实验室研究探索阶段,正在进行临床实验或批准应用还不多。已经获得批准的主要是皮肤产品、软骨及骨产品、心血管产品、神经系统产品、人工器官等,其临床应用较多。今后将会有越来越多的组织工程产品面世,其临床应用也会越来越广泛。     

组织工程的诞生与发展——组织工程连载之一

传统器官移植受到器官来源、伦理以及机体免疫排斥等方面的限制而难以满足临床治疗需要。为了应对不断的挑战,组织工程得以诞生和发展。最初组织工程的含义是联合使用细胞、支架材料和生物活性因子以促进组织的修复和再生方面的研究和应用,随着研究的深入组织工程的概念得到不断发展。现代组织工程学是一门利用工程学和生命科学的原理,研究和开发具有生物活性的人工替代物,以维持、恢复或提高人体受损组织的功能的交叉学科。自诞生20多年来,组织工程的发展大致经历了三个阶段。再生医学是现代临床医学的重要分支,与干细胞和组织工程具有密切的联系。组织工程是完美的组织器官再生,是再生医学的关键研究领域,体现了再生医学的主要发展方向。再生医学的理论和技术方法促进了组织工程的发展。     

重要生命器官组织工程研究

组织、器官的丧失或功能障碍是人类健康所面临的主要危害之一,也是引起人类疾病和死亡的最主要原因。如何从根本上解决组织、器官缺损或功能障碍,也已成为科学界特别是生命科学领域所要积极探索的国际性前沿课题。组织工程的最终目的是工程化生产可以用于替代人体不可逆损伤的、功能退化的组织和器官,使更多的患者得到及时治疗,为根本解决人体重要生命器官的疾病带来新的途径,从而提高人类的健康水平和生活质量。经过研究人员20余年的不懈努力,组织工程研究领域取得了长足的进步。其中,重要生命器官的组织工程研究目前已经成为组织工程研究领域的热点和焦点,并且针对心脏、肝脏、肾脏、胰腺等重要生命器官的组织工程研究正在不断取得突破。该文从干细胞定向可控分化、功能化支架材料仿生制备、重要生命器官体外构建与应用以及基于快速成型和微制造技术的器官精准设计与制造等方面,综述了国内外重要生命器官组织工程研究最新进展及相关的产业化情况,希望为重要生命器官组织工程研究和产业化开发提供一定的参考。     

联合细胞培养在组织工程血管化中的应用

自从1987年正式提出组织工程这一概念来以来,培养具有生物学活性组织器官替代物始终是组织工程学的发展方向。目前,虽然一些工程化组织如皮肤、软骨等已被成功构建,并应用于临床,但其他工程化组织如心脏、骨骼肌、肝脏等体积大、功能复杂,移植后难以及时建立血液供应。而及时建立的血管网络对组织器官的存活与功能实现至关重要。为此,国内外一些实验室采用联合细胞培养的方法,观察不同细胞间的相互作用对血管形成的影响。结果表明,联合细胞培养在血管的形成、稳定和成熟方面起着重要作用。     

内皮祖细胞及其在组织工程中的应用

目前,组织工程化血管的构建和工程化组织器官的血管化因内皮种子细胞的扩增能力不足和生物活性不强而受到限制。内皮祖细胞(EPC)是内皮细胞的前体细胞。出生后,EPC主要存在于骨髓,可向外周血液缓慢释放,参与机体缺血组织的血管重建和损伤血管的重新内皮化。现对EPC的来源、分布、表型特征、动员、分化、归巢、分离、培养与鉴定等生物学特性和EPC在组织工程中的应用进行了全面的综述,并指出目前存在的问题和研究方向。     

组织工程的突破与挑战——组织工程国家工程中心科研进展

组织工程技术已被普遍认为是解决组织、器官缺损修复与功能重建的有效手段,它的飞速发展依赖于细胞学、材料学、工程学、临床医学等多学科的交叉渗透.作为组织工程的三大核心,种子细胞、生物材料、组织构建各方面的突破,为组织工程技术的发展奠定了基础.组织工程国家工程中心近年来围绕上述核心开展了系列研究,通过研究胚胎干细胞、成体干细胞、同种异体干细胞、以及发育同源细胞替代的探索,为解决种子细胞来源问题提供了多种选择;生物支架材料的开发,为细胞增殖分化、组织再生提供理想的支持与空间,而生物反应器的开发与应用,进一步提高了组织构建技术,为促进组织的体外形成、重塑和功能成熟创造了条件.在此基础上,开展了大动物体内组织构建和缺损修复的研究,形成了以应用为目标的研究特色,并成功将部分技术应用于临床治疗.本文将对组织工程国家工程中心已有进展做简单介绍并对面临的挑战进行分析.     

组织器官三维构建及原位组织工程概念——组织工程连载之四

组织器官三维构建就是把种子细胞和支架材料结合而获得设计的组织或器官,属于组织工程的核心内容,也最能体现组织工程的技术水平,如血管、气管的构建。由于传统组织工程存在缺陷,Shimizu于1998年首先提出了原位组织工程的概念,它是运用组织工程学基本原理,通过各种方法诱导移植的外源性的种子细胞或内源性的缺损组织局部细胞发生迁移、增殖、分化形成新生组织修复缺损。原位组织工程最大的特点是不依赖体外的细胞培养装置--生物反应器。原位组织工程是传统离体组织工程的有益补充。离体组织工程仍具有广阔的发展前景。     

间充质干细胞向内皮细胞的分化及其在血管组织工程中的应用

利用间充质干细胞(menchymal stem cells,MSCs)的多向分化能力,将其诱导成为内皮细胞(endothelial cells,ECs),可解决血管组织工程中自体血管细胞作为种子细胞所面临的细胞来源及成体细胞增殖能力有限的问题.MSCs可从多种组织中分离获得,目前应用于血管组织工程的3种MSCs主要源于骨髓、脂肪和肌肉.MSCs的分化可由多种刺激触发,在其向ECs的分化过程中生长因子、支架性质和机械应力等因素起着重要的作用.而以MSCs分化为ECs为基础的组织工程血管在动物模型中展现出促血管生成能力和良好的通畅性,但目前其在临床上的应用较少,需进一步研究,并有许多问题仍待探究.     

组织工程面临的技术挑战与发展趋势

当前组织工程研究仍处于初级阶段,还仅仅是初步应用组织工程技术修复临床简单组织缺损,还有许多制约组织工程应用与发展的基本科学问题没有阐明.随着组织工程各个层面技术难题的逐个攻破,组织工程的内涵和外延将不断拓展,并有助于加快组织工程的产业化进程,促进临床应用.针对组织工程核心要素研究的不足,结合最新的组织工程研究进展,阐述...     

Tissue engineering in otorhinolaryngology

Tissue engineering is a field of research with interdisciplinary cooperation between clinicians, cell biologists, and materials research scientists. Many medical specialties apply tissue engineering techniques for the development of artificial replacement tissue. Stages of development extend from basic research and preclinical studies to clinical application. Despite numerous established tissue replacement methods in otorhinolaryngology, head and neck surgery, tissue engineering techniques opens up new ways for cell and tissue repair in this medical field. Autologous cartilage still remains the gold standard in plastic reconstructive surgery of the nose and external ear. The limited amount of patient cartilage obtainable for reconstructive head and neck surgery have rendered cartilage one of the most important targets for tissue engineering in head and neck surgery. Although successful in vitro generation of bioartificial cartilage is possible today, these transplants are affected by resorption after implantation into the patient. Replacement of bone in the facial or cranial region may be necessary after tumor resections, traumas, inflammations or in cases of malformations. Tissue engineering of bone could combine the advantages of autologous bone grafts with a minimal requirement for second interventions. Three different approaches are currently available for treating bone defects with the aid of tissue engineering: (1) matrix-based therapy, (2) factor-based therapy, and (3) cell-based therapy. All three treatment strategies can be used either alone or in combination for reconstruction or regeneration of bone. The use of respiratory epithelium generated in vitro is mainly indicated in reconstructive surgery of the trachea and larynx. Bioartificial respiratory epithelium could be used for functionalizing tracheal prostheses as well as direct epithelial coverage for scar prophylaxis after laser surgery of shorter stenoses. Before clinical application animal experiments have to prove feasability and safety of the different experimental protocols. All diseases accompanied by permanently reduced salivation are possible treatment targets for tissue engineering. Radiogenic xerostomia after radiotherapy of malignant head and neck tumors is of particular importance here due to the high number of affected patients. The number of new diseases is estimated to be over 500,000 cases worldwide. Causal treatment options for radiation-induced salivary gland damage are not yet available; thus, various study groups are currently investigating whether cell therapy concepts can be developed with tissue engineering methods. Tissue engineering opens up new ways to generate vital and functional transplants. Various basic problems have still to be solved before clinically applying in vitro fabricated tissue. Only a fraction of all somatic organ-specific cell types can be grown in sufficient amounts in vitro. The inadequate in vitro oxygen and nutrition supply is another limiting factor for the fabrication of complex tissues or organ systems. Tissue survival is doubtful after implantation, if its supply is not ensured by a capillary network.     

Tissue engineering in female pelvic floor reconstruction

Pelvic organ prolapse is a common and frequently occurring disease in middle‐aged and elderly women. Mesh implantation is an ideal surgical treatment. The polypropylene mesh commonly used in clinical practice has good mechanical properties, but there are long‐term complications. The application of tissue engineering technology in the treatment of pelvic organ prolapse disease can not only meet the mechanical requirements of pelvic floor support, but also be more biocompatible than traditional polypropylene mesh, and can promote tissue repair to a certain extent. In this paper, the progress of tissue engineering was summarized to understand the application of tissue engineering in the treatment of pelvic organ prolapse disease and will help in research.     

黄鳝的泌尿系统及其功能

黄鳝腹腔左侧有盲端的中空管状结构,不是退化性腺,而是十分特化的长管囊膀胱。膀胱内壁具大量发达的绒毛,绒毛表面是移行上皮。在绒毛内部或基部有丰富的血管,因此该管囊膀胱不仅可贮存尿液,而且可能对水分等有重吸收作用。在中肾管与膀胱相接处,膀胱腔背侧出现一条明显的纵行皱襞,即在其横切面上观为巨绒毛。巨绒毛形成的原因,主要是中肾管移入膀胱壁所致。中肾管在巨绒毛内移行一程后才开口于膀胱。因此,黄鳝的生殖腺不是一对,而是一个,位于腹腔右侧。黄鳝肾脏细长,呈“丫”,在腹腔背侧,紧贴脊椎。前端为头肾,无肾单位,仅是造血器官。中肾有类似于哺乳类的肾小体,但数量较少,主要分布在肾脏周缘。肾小管包括颈段、初级近曲小管、次级近曲小管、初级远曲小管和次级远曲小管。两中肾管位于两肾叶腹内侧,其上皮间或是假复层柱状上皮,间或是移行上皮。前者含有许多杯状细胞,并可见到顶浆分泌的现象。中肾的肾小管间组织是大量的红细胞样组织,头肾似具有贮存或释放刚成熟的红细胞的组织结构,因此黄鳝肾脏可能是体内主要的造血器官。     

Strategies for organ level tissue engineering

The field of tissue engineering has made considerable strides since it was first described in the late 1980s. The advent and subsequent boom in stem cell biology, emergence of novel technologies for biomaterial development, and further understanding of developmental biology have contributed to this accelerated progress. However, continued efforts to translate tissue engineering strategies into clinical therapies have been hampered by the problems associated with scaling up laboratory methods to produce large, complex tissues. The significant challenges faced by tissue engineers include the production of an intact vasculature within a tissue-engineered construct and recapitulation of the size and complexity of a whole organ. Here we review the basic components necessary for bioengineering organs – biomaterials, cells and bioactive molecules–and discuss various approaches for augmenting these principles to achieve organ level tissue engineering. Ultimately, the successful translation of tissue-engineered constructs into everyday clinical practice will depend upon the ability of the tissue engineer to “scale up” every aspect of the research and development process.     

慢性肾功能衰竭的治疗现状及研究前景

CRF是威胁人类健康及生命的常见病之一,近年来平均每年以约8%的速度在增长。依靠慢性肾功能衰竭肾脏母体及机体的再生潜能在脱细胞基质支架上修复重建肾脏结构与功能,这将是慢性肾功能衰竭治疗的一种全新的途径。而去细胞基质在组织工程、干细胞及再生医学的大量应用为解决组织器官的修复和重建等难题带来了希望。本文就目前CRF的治疗现状及、肾脏组织工程研究前景进行简要综述。     

Human lung tissue engineering: a critical tool for safer medicines

In the field of human tissue-engineering, there has been a strong focus on the clinical aspects of the technology, i.e. repair, replace and enhance a given tissue/organ. However, much wider applications for tissue engineering (TE) exist outside of the clinic that are often not recognised, and include engineering more relevant models than animals in basic research and safety testing. Traditionally, research is initially conducted on animals or cell lines, both of which have their limitations. With regard to cell lines, they are usually transformed to enable indefinite proliferation. These immortalised cell lines provide the researcher with an almost limitless source of material. However, the pertinence of the data produced is now under scrutiny, with the suggestion that some historical cell lines may not be the cell type originally reported. By engineering normal, biomimetic (i.e. life-mimicking), human tissues with defined physiology (i.e. human tissue equivalents), the complex 3-dimensional (3-D) tissue/organ physiology is captured in vitro, providing the opportunity to directly replace the use of animals in research/testing with more relevant systems. Therefore, it is imperative that testing strategies using organotypic models are developed that can address the limitations of current animal and cellular models and thus improve drug development, enabling faster delivery of drugs which are safer, more effective and have fewer side effects in humans.     

Strategies for organ level tissue engineering

The field of tissue engineering has made considerable strides since it was first described in the late 1980s. The advent and subsequent boom in stem cell biology, emergence of novel technologies for biomaterial development and further understanding of developmental biology have contributed to this accelerated progress. However, continued efforts to translate tissue-engineering strategies into clinical therapies have been hampered by the problems associated with scaling up laboratory methods to produce large, complex tissues. The significant challenges faced by tissue engineers include the production of an intact vasculature within a tissue-engineered construct and recapitulation of the size and complexity of a whole organ. Here we review the basic components necessary for bioengineering organs-biomaterials, cells and bioactive molecules-and discuss various approaches for augmenting these principles to achieve organ level tissue engineering. Ultimately, the successful translation of tissue-engineered constructs into everyday clinical practice will depend upon the ability of the tissue engineer to "scale up" every aspect of the research and development process.     

The challenge of translating ischemic conditioning from animal models to humans: the role of comorbidities

Following a period of ischemia (local restriction of blood supply to a tissue), the restoration of blood supply to the affected area causes significant tissue damage. This is known as ischemia-reperfusion injury (IRI) and is a central pathological mechanism contributing to many common disease states. The medical complications caused by IRI in individuals with cerebrovascular or heart disease are a leading cause of death in developed countries. IRI is also of crucial importance in fields as diverse as solid organ transplantation, acute kidney injury and following major surgery, where post-operative organ dysfunction is a major cause of morbidity and mortality. Given its clinical impact, novel interventions are urgently needed to minimize the effects of IRI, not least to save lives but also to reduce healthcare costs. In this Review, we examine the experimental technique of ischemic conditioning, which entails exposing organs or tissues to brief sub-lethal episodes of ischemia and reperfusion, before, during or after a lethal ischemic insult. This approach has been found to confer profound tissue protection against IRI. We discuss the translation of ischemic conditioning strategies from bench to bedside, and highlight where transition into human clinical studies has been less successful than in animal models, reviewing potential reasons for this. We explore the challenges that preclude more extensive clinical translation of these strategies and emphasize the role that underlying comorbidities have in altering the efficacy of these strategies in improving patient outcomes.KEY WORDS: Comorbidities, Ischemic postconditioning, Ischemic preconditioning, Remote ischemic preconditioning