脐血间充质干细胞向肝细胞分化的研究进展

随着对脐血干细胞的不断认识，研究者们发现脐血中含有丰富的造血干细胞。自1988年Gluckman等首次报道脐血移植治疗范科尼病以来，脐血移植已成为治疗恶性及非恶性血液系统疾病的重要方法之一。脐血干细胞的研究得到了人们的重视，世界各地已经建立了许多脐血库。2000年Erices等通过研究发现脐血中还存在有在细胞形态、免疫表型及功能特点方面与骨髓间充质干细胞相似的一类同质细胞群。自此脐血间充质干细胞（umbilical cord blood-mesenchyrmal stem cell，UCB-MSC）引起广泛关注。同时关于UBC-MSC分化能力的研究也逐步展开，现对脐血间充质干细胞及其向肝细胞的分化作一综述。     

脐血间充质干细胞治疗肝衰竭的研究进展

肝干细胞按其来源可划分为肝源性干细胞和非肝源性干细胞,而非肝源性肝干细胞主要指骨髓间充质干细胞、脂肪间充质干细胞、脐带间充质干细胞和脐血间充质干细胞等,脐血间充质干细胞作为非肝源性肝干细胞的一种,具有低免疫原性、来源丰富、可扩增及多向分化的特点,在诱导剂的作用下可向肝细胞分化,表达肝细胞特异性标志物及相关功能,这为移植脐血间充质干细胞治疗肝衰竭提供了实验依据。     

脐血造血干细胞移植的临床研究进展

脐血已逐渐成为异基因造血干细胞移植治疗中的一个重要的干细胞来源.尽管移植后感染相关病死率稍高,但由于脐血容易获得、 移植后移植物抗宿主病的发生率低等优点,脐血移植患者的存活率与其他类型的造血干细胞移植相当.脐血移植技术的不断改善也给患者带来了较好的疗效,脐血的临床应用为多种难治性疾病的治疗提供了新的方法.现就近年来脐血...     

成体干细胞在体外培养扩增中的自发恶性转化

干细胞的研究方兴未艾。由于胚胎干细胞涉及伦理问题,所以成体干细胞研究倍受关注,其中间充质干细胞是目前研究最为广泛而深入的一类成体干细胞。已证实骨髓、皮肤真皮、脂肪、肌肉、骨膜等多种组织中存在间充质干细胞。大量实验研究和部分临床试用结果均显示,间充质干细胞移植对造血恢复、创面愈合、骨和软骨组织置换、心肌和骨骼肌修复、血管修复以及一些神经系统疾病的治疗,前景良好。我们自己的研究还发现间充质干细胞移植可同时实现促进造血恢复和创伤愈合的双重作用。     

脐血造血干细胞移植的相关免疫分析

脐血造血干细胞移植融化疗与免疫治疗于一体,作为血液恶性疾病的治疗手段已获公认,其重要原因就是脐血造血干细胞移植比其他造血干细胞移植具有诸多优点:来源丰富、取材简单;对供、受者HLA相符的要求相对较低;不易受病毒及残留肿瘤细胞的污染;CD3、CD4相对不成熟,GVHD发生率低;NK细胞、LAK细胞较多,GVL发生率低;增殖、自我增殖能力强;骨髓基质细胞多,给造血干细胞提供生长的微环境等.     

脐带血和成人外周血LTT及T亚群的区别

造血干细胞移植正日益广泛地用于各种肿瘤、白血病及某些遗传性疾病的治疗,由于脐血中造血干细胞含量高,加之脐血来源丰富,采集、保存简便,免疫源性低,容易克服组织相容性障碍,被认为是骨髓以外另一个极有潜力的造血干细胞移植的造血细胞来源.为此,我们对脐血淋巴细胞转化功能和T亚群进行了检测,以探讨脐血的免疫特性.     

骨髓间充质干细胞的研究进展

骨髓间充质干细胞(MSCs)是目前倍受关注的一类具有多向分化潜能的成体干细胞,其广泛分布于各种不同的组织中,如骨髓、外周血、脐血、脂肪、胎肺、胎肾等组织。MSCs可分化为成骨细胞、成软骨细胞、脂肪细胞、神经细胞、肌肉细胞等多种组织细胞。另外,MSCs还能够支持造血,对造血干细胞有扩增作用,共移植造血干细胞和MSCs可以促进造血干细胞的植入。临床上MSCs可望应用于组织工程、细胞工程、基因治疗、细胞因子替代治疗等领域[1]。本文对MSCs的来源、生物学特性、分离纯化与培养、多分化潜能以及应用前景作一综述。1来源1.1骨髓:目前…     

人脐带间充质干细胞的生物学特性及其在血液系统疾病中的应用

间充质干细胞是一种具有自我更新和多向分化能力的成体干细胞,在组织工程、基因治疗和造血干细胞移植领域具有较好的应用前景。骨髓是间充质干细胞的经典来源。近年研究显示,人脐带中也存在大量间充质干细胞,由于脐带来源间充质干细胞具有来源广泛、取材方便、相对纯净、含量丰富以及免疫原性低等优点,正逐渐成为间充质干细胞研究领域的热点之一。本文就其生物学特征、优势以及在血液系统疾病中的应用前景等予以综述。     

静脉输注脐血干细胞移植的护理进展

自法国Gluckman等1988年采用同胞脐带血移植治愈儿童范可尼贫血以来，全世界已有3万多例患者成功实施了脐血干细胞移植。干细胞具有再生为各种组织器官的潜能，被称为“万能细胞”。脐血（umbilical cord blood，UCB）已成为除骨髓以外的重要间充质干细胞（mesenchy-mal stem cells，MSCs）来源，是细胞替代治疗理想的种子细胞［1］。目前很多疾病，都可借助干细胞技术进行治疗。脐血干细胞排异反应小，再生能力和速度是成人造血干细胞的10～20倍。因此，在配型和移植方面具有更高的成功率。如何保证每份细胞数量有限的脐血安全、有效地输注到患者体内，确保达到植入要求非常重要。本文对脐血干细胞移植的特点、冷冻保存、复温、不良反应和静脉输注等相关护理问题进行综述。     

脐血造血干细胞移植的研究进展

自1980年以来,人们认识到脐血中含有丰富的造血干细胞,并用造血干细胞移植治疗血液系统疾病及其他各种相关疾病,得到了更好的效果,脐带血因其更容易广泛获取,又没有伦理道德的限制,而且有立即可用性、移植免疫耐受较低等诸多优点被广泛利用,从此在移植医学和再生医学领域获得了一席之地。脐血的收集和移植得到了很快的发展,脐血库应运而生。该文就目前脐血库的现状和脐血造血干细胞移植的应用进展进行综述。     

Umbilical cord blood: lessons learned and lingering challenges after more than 20 years of basic and clinical research

During the last 23 years, cord blood research has played important roles both in experimental and clinical hematology. Cord blood-derived hematopoietic stem and progenitor cells have been shown to possess particular biological features and their study has been very important in our understanding of hematopoietic development. Today, >20,000 umbilical cord blood (UCB) transplants have been performed worldwide and ～460,000 UCB units are being stored in >47 UCB banks worldwide. Here a brief overview on some of the most relevant issues regarding cord blood research is presented.     

No longer a biological waste product: umbilical cord blood

Haematopoietic stem cell transplantation is an accepted curative therapy for many cancers and inherited non-malignant diseases, including bone marrow failure syndromes, haemoglobinopathies, and inborn errors of metabolism. Stem cells can be used from the bone marrow or blood of matched siblings or appropriately matched unrelated volunteers, but many patients do not have a suitably matched donor. Umbilical cord blood (UCB) has been successfully used as an alternative stem cell source. It has the advantage of tolerance for a degree of human leukocyte antigen (HLA) incompatibility not possible with adult bone marrow, resulting in greater likelihood of finding an appropriate match. UCB is also stored fully tested and cryopreserved, leading to rapid availability. Greatest clinical experience in UCB transplants has been in treating paediatric leukaemia. Results using well matched UCB grafts are equivalent or better than with unrelated bone marrow transplant. Cell dose and the degree of HLA matching are critical determinants in the success of UCB transplant. The use of UCB in older children and adult patients has been limited by the fixed, low cell dose available in a UCB unit, relative to recipient weight. This can be overcome by strategies such as using two or more UCB units. Early animal studies suggest that UCB may have the potential to differentiate into other cell types, including nervous tissue, and may in future play a role in the treatment of disorders such as Alzheimer disease and Parkinson disease.     

脐血干细胞的免疫学特性概述

脐血来源丰富,避免了一些伦理问题。脐血干细胞表面表达人类白细胞抗原(HLA)Ⅰ类分子,存在但不表达HLAⅡ类分子,在多向分化过程中始终不表达HLAⅡ类分子,产生免疫逃避反应,移植入体内可以产生免疫抑制。经多种免疫刺激因子均不产生或较少产生免疫反应,这种免疫反应并不影响脐血干细胞和生物学效应。脐血具有抑制T细胞活性和调节免疫反应,并具有免疫抑制的调节能力。脐血干细胞可作为临床组织工程的来源细胞。     

脐血和成人外周血细胞免疫活性的区别

脐血中富含多种造血细胞，可移植治疗实体瘤等疾病。本文采用间接免疫荧光法与淋巴细胞转化试验，比较脐血与成人外周血Ｔ细胞亚群和淋巴细胞转化率。结果显示脐带血ＣＤ_３~＋、ＣＤ_８~＋细胞百分率较成人外周血低（Ｐ＜０．００１），脐血淋巴细胞转化率低。提示进行脐血移植导致移植物抗宿主病（ＧＶＨＤ）的发生率和反应程度均较成人低。     

骨髓基质干细胞治疗神经系统疾病的研究现状

骨髓基质干细胞(mesenchymal stem cells,MSCs)具有分化为多种细胞的潜能,可以从鼠和人的骨髓中获得,可以通过多种途径植入脑内。MSCs可以选择性地靶向作用于损伤组织,激活内源性的反应机制,从而促进神经系统损伤功能的恢复。在供、受体之间可能存在几种作用机制,包括:受体对植入MSCs的免疫应答、指导MSCs在受体内分化和向损伤靶点的归巢机制以及局部微环境的作用。MSCs植入可以看作是一种有极大潜力的治疗神经系统疾病的细胞疗法,目前在临床前和部分临床试验中用于包括脑和脊髓损伤、脑缺血、神经系统变性疾病的治疗。本文对近期MSCs在神经系统疾病的应用简要综述如下。     

造血干细胞的血管分化及其在肢体缺血性疾病中的治疗作用

造血干细胞是最早发现、研究最深入的组织干细胞,造血干细胞移植已成功治疗了多种血液及免疫性疾病.很早以前,有人推测造血干细胞和血管干细胞来自共同的干细胞-血液血管母细胞.近年研究显示,造血干细胞具有分化血管内皮细胞的能力.动物实验显示,缺血部位造血干细胞移植可以促进血管新生,改善肢体缺血.临床小规模试验研究表明,应用骨髓和外周血造血干细胞移植可以显著促进缺血下肢的血管重建.本文简要介绍骨髓、外周血、脐血造血干细胞的血管分化功能及其在肢体缺血性疾病中的治疗作用.     

间充质干细胞的免疫调节功能

间充质干细胞(MSC)在支持造血细胞的成熟、分化和生存方面具有重要作用.最近研究发现,MSC具有免疫调节作用,能抑制树突状细胞(DC)成熟,并通过细胞-细胞接触的机制,抑制T淋巴细胞、B淋巴细胞及自然杀伤细胞(NK细胞)的功能,在自身免疫性疾病及肿瘤细胞免疫逃逸中至关重要.现正尝试将MSC用于抗急性移植物抗宿主病(aGVHD)及自身免疫性疾病的治疗.     

Retinal stem cells and potential cell transplantation treatments

The retina, histologically composed of ten delicate layers, is responsible for light perception and relaying electrochemical signals to the secondary neurons and visual cortex. Retinal disease is one of the leading clinical causes of severe vision loss, including age-related macular degeneration, Stargardt's disease, and retinitis pigmentosa. As a result of the discovery of various somatic stem cells, advances in exploring the identities of embryonic stem cells, and the development of induced pluripotent stem cells, cell transplantation treatment for retinal diseases is currently attracting much attention. The sources of stem cells for retinal regeneration include endogenous retinal stem cells (e.g., neuronal stem cells, Müller cells, and retinal stem cells from the ciliary marginal zone) and exogenous stem cells (e.g., bone mesenchymal stem cells, adipose-derived stem cells, embryonic stem cells, and induced pluripotent stem cells). The success of cell transplantation treatment depends mainly on the cell source, the timing of cell harvesting, the protocol of cell induction/transplantation, and the microenvironment of the recipient's retina. This review summarizes the different sources of stem cells for regeneration treatment in retinal diseases and surveys the more recent achievements in animal studies and clinical trials. Future directions and challenges in stem cell transplantation are also discussed.     

Expansive effects of aorta-gonad-mesonephros-derived stromal cells on hematopoietic stem cells from embryonic stem cells

Background Hematopoietic stem cells (HSCs) give rise to all blood and immune cells and are used in clinical transplantation protocols to treat a wide variety of refractory diseases, but the amplification of HSCs has been difficult to achieve in vitro. In the present study, the expansive effects of aorta-gonad-mesonephros (AGM) region derived stromal cells on HSCs were explored, attempting to improve the efficiency of HSC transplantation in clinical practice.Methods The murine stromal cells were isolated from the AGM region of 12 days postcoitum (dpc) murine embryos and bone marrow（BM）of 6 weeks old mice, respectively. After identification with flow cytometry and immunocytochemistry, the stromal cells were co-cultured with ESCs-derived, cytokines-induced HSCs. The maintenance and expansion of ESCs-derived HSCs were evaluated by detecting the population of CD34+ and CD34+Sca-1+cells with flow cytometry and the blast colony-forming cells (BL-CFCs), high proliferative potential colony-forming cells (HPP-CFCs) by using semi-solid medium colonial culture. Finally, the homing and hematopoietic reconstruction abilities of HSCs were evaluated using a murine model of HSC transplantation in vivo.Results AGM and BM-derived stromal cells were morphologically and phenotypically similar, and had the features of stromal cells. When co-cultured with AGM or BM stromal cells, more primitive progenitor cells (HPP-CFCs ) could be detected in ESCs derived hematopoietic precursor cells, but BL-CFC’s expansion could be detected only when co-cultured with AGM-derived stromal cells. The population of CD34+ hematopoietic stem/progenitor cells were expanded 3 times,but no significant expansion in the population of CD34+Sca-1+ cells was noted when co-cultured with BM stromal cells. While both CD34+ hematopoietic stem/progenitor cells and CD34+Sca-1+ cells were expanded 4 to 5 times respectively when co-cultured with AGM stromal cells. AGM region-derived stromal cells, like BM-derived stromal cells, could promote hematopoietic reconstruction and HSCs’ homing to BM in vivo.Conclusions AGM-derived stromal cells in comparison with the BM-derived stromal cells could not only support the expansion of HSCs but also maintain the self-renewal and multi-lineage differentiation more effectively. They are promising in HSC transplantation. Chin Med J 2005; 118(23):1979-1986