骨骼肌成肌细胞移植治疗缺血性心脏病的研究进展和临床前景

干细胞是一类具有自我更新和多向分化潜能的原始细胞,根据来源的不同,可分为胚胎干细胞和成体干细胞.人类胚胎干细胞已成功地在体外培养,但由于其异源性、可能致癌性及伦理道德方面等问题[1],限制了其进一步研究及临床应用.而成体干细胞自体移植避免了免疫排斥和伦理道德问题,其实用性非常广泛.目前可供移植的成体干细胞包括骨骼肌成肌细胞,骨髓间充质干细胞,内皮祖细胞等.     

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。     

干细胞治疗心血管疾病现状及展望

心脏仅有有限的自我再生能力,因此,心肌受损或梗死后的治疗需要外源性的细胞加以修复,目前研究最多的是干细胞治疗。干细胞按来源不同分为胚胎干细胞和成体干细胞。胚胎干细胞研究由于伦理学上的争议,其研究受到困扰,成体干细胞移植成为研究热点。研究表明干细胞移植后,心脏的功能有改善,但其具体机制是移植细胞自身作用,还是细胞旁分泌作用或其他,各研究提供的证据不一。移植本身亦带来了许多问题,如移植手段,移植细胞的纯度、移植后细胞的协调性、机体的排斥、致心律失常作用等,这些都引发了进一步的研究。     

骨髓间充质干细胞的研究进展及其应用前景

干细胞是一类具有自我更新和分化潜能的细胞群体,最新的分类方法是根据其来源将其分为四类:成体干细胞、胎儿干细胞、胚胎干细胞和核移植干细胞。胚胎性干细胞和成体干细胞除了来源不同,其最大的区别在于增殖能力和分化潜能的不同:胚胎性干细胞可无限增殖,而成体干细胞的增殖能力则有限;胚胎性干细胞分化潜能要较成体干细胞宽。成体干细胞的可塑性已经成为研究热点,目前有越来越多的实验结果都证实成体干细胞确实具有分化为多种细胞类型的潜能,因此成体干细胞成为生物医学领域中一个很好的研究手段,同时具有广阔的临床应用前景。成体骨髓来…     

牙周膜干细胞的研究进展

根据干细胞的来源可分为胚胎干细胞和成体干细胞,由于利用胚胎干细胞面临复杂的伦理学问题,因而对成体干细胞的研究就具有深远的意义〔1〕。牙周膜干细胞(PDLSC)是牙周组织中具有自我复制和高度增殖能力的一类成体干细胞。PDLSC具有分化成牙槽骨,牙骨质和牙周膜潜能,在牙周病的     

肝干细胞研究进展

绝大多数肝干细胞的研究集中在胚胎来源肝干细胞或卵圆细胞。最近研究人员从成体肝脏中鉴定并分离出肝祖细胞,这些细胞也有着双向分化潜能并能多次分裂,从而使肝于细胞定义更加复杂。目前,存在于成体的干／祖细胞群的作用尚未明确,关于对干细胞分化和器官发育的过程的理解亦存在分歧。本文重点讨论从不同发育阶段肝组织中分离的或损伤模型反应性产生的多种肝脏来源干细胞或祖细胞群。     

甲状腺干细胞的研究进展

甲状腺干细胞是一类具有自我复制能力及具有向甲状腺细胞分化潜能的未分化细胞.近年来,关于甲状腺干细胞的研究日益成熟,已经成功地从胚胎干细胞、甲状腺成体干细胞和骨髓干细胞诱导分化出甲状腺滤泡细胞,这类细胞能够表达甲状腺特征性基因,并具有摄碘功能.甲状腺干细胞的研究为临床甲状腺疾病的治疗,特别是甲状腺干细胞移植奠定了基础.     

内皮祖细胞与缺血性心血管病

内皮祖细胞(EPCS)是一种能分化为血管内皮细胞的前体细胞,也称为成血管母细胞,是一种成体干细胞.近期研究发现,EPCS不仅参与胚胎血管生成(vascuLlogenesis),也参与出生后的血管新生(angiogenesis),提示EPCS在缺血性疾病中可能有重要意义. 　　……     

Oct4在干细胞和肿瘤细胞中的表达

干细胞按分化能力分为全能性、多能性和专能性干细胞。Oct4是全能性或多能性干细胞标记物,在胚胎干细胞、胚胎生殖细胞和胚胎／生殖细胞肿瘤中阳性表达,但在分化的组织中均表达降低或消失,提示其在胚胎干细胞、生殖细胞和胚胎／生殖肿瘤中的表达与这些细胞的多能性分化特性密切相关。在成体组织和体细胞肿瘤中亦发现Oct4阳性表达。迄今为止,Oct4在成体组织中的表达主要局限于具有干细胞特性的细胞,如皮肤基底细胞层中的个别细胞、乳腺干细胞和胃干细胞等。本文简要综述Oct4在胚胎干／生殖细胞、成体和肿瘤组织中表达的研究现状,并对其在成体肿瘤中的表达及与肿瘤干细胞的关系进行讨论。     

脐血干细胞向肝系细胞分化的研究进展

干细胞是一类具有自我增殖能力和多向分化潜能的细胞,按照其来源可以分为胚胎干细胞(embry- onic stem cells,ESC)和成体干细胞(somatic／adult stem cells)。ESCS来源于人或动物的胚胎内细胞团或原始生殖嵴,在体内外能分化为三个胚层的所有组织细胞,但其研究及应用受到伦理学的限制。成体干细胞是分布在已分化特定组织中的未分化细胞,它具有自我更新的能力,并能产生由它来源的所有特定类型的组织细胞,其来源包括骨髓、血液、肝脏、皮肤等。目前研究发现,成体干细胞不仅能生成其来源组织的所有特化细胞,还能分化为其它组织的细胞,即所谓的“横向分化”(trans-differentia- tion)。     

Stem and progenitor cell systems in liver development and regeneration

The liver comprises two stem/progenitor cell systems: fetal and adult liver stem/progenitor cells. Fetal hepatic progenitor cells, derived from foregut endoderm, differentiate into mature hepatocytes and cholangiocytes during liver development. Adult hepatic progenitor cells contribute to regeneration after severe and chronic liver injuries. However, the characteristics of these somatic hepatic stem/progenitor cells remain unknown. Culture systems that can be used to analyze these cells were recently established and hepatic stem/progenitor cell‐specific surface markers including delta‐like 1 homolog (DLK), cluster of differentiation (CD) 13, CD133, and LIV2 were identified. Cells purified using antibodies against these markers proliferate for an extended period and differentiate into mature cells both in vitro and in vivo. Methods to force the differentiation of human embryonic stem and induced pluripotent stem (iPS) cells into hepatic progenitor cells have been recently established. We demonstrated that the CD13⁺CD133⁺ fraction of human iPS‐derived cells contained numerous hepatic progenitor‐like cells. These analyses of hepatic stem/progenitor cells derived from somatic tissues and pluripotent stem cells will contribute to the development of new therapies for severe liver diseases.     

脂肪组织来源干细胞治疗缺血性心脏病的研究进展

干细胞移植治疗心血管疾病尤其是缺血性心脏病取得了令人鼓舞的结果,但既往研究主要集中于胚胎干细胞和骨髓间充质干细胞的研究。近年来,人们发现脂肪组织来源干细胞（ASCs）与其他组织来源干细胞相比具有来源广、取材创伤小、具有多向分化潜能、增殖能力强等优点,故近几年来ASCs在心血管疾病治疗上的作用受到越来越多的重视。本文对ASCs细胞生物学特性以及ASCs作为种子干细胞在缺血性心脏病、心肌细胞再生方面的基础和临床研究进展作一综述。     

血管内皮祖细胞在心血管疾病中的研究进展

血管内皮祖细胞是血管内皮细胞的前体细胞,又称为血管母细胞。不仅参与胚胎血管生成,也参与出生后的血管发生过程。应用血管内皮祖细胞进行细胞移植是目前治疗缺血性血管病变的研究热点,已有报道开始应用于临床。现就血管内皮祖细胞在心血管疾病中的研究现状做一综述,同时对干细胞移植存在的安全性、靶向性、效应性方面的问题以及如何开发一种新型的干细胞移植技术做一评价和展望。     

Resident cardiac progenitor cells: At the heart of regeneration

Stem cell therapy has recently emerged as an innovative strategy over conventional cardiovascular treatments to restore cardiac function in patients affected by ischemic heart disease. Various stem cell populations have been tested and their potential for cardiac repair has been analyzed. Embryonic stem cells retain the greatest differentiation potential, but concerns persist with regard to their immunogenic and teratogenic effects. Although adult somatic stem cells are not tumourigenic and easier to use in an autologous setting, they exist in small numbers and possess reduced differentiation potential. Traditionally the heart was considered to be a post-mitotic organ; however, this dogma has recently been challenged with the identification of a reservoir of resident stem cells, defined as cardiac progenitor cells (CPCs). These endogenous progenitors may represent the best candidates for cardiovascular cell therapy, as they are tissue-specific, often pre-committed to a cardiac fate, and display a greater propensity to differentiate towards cardiovascular lineages. This review will focus on current research into the biology of CPCs and their regenerative potential. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".     

骨髓间质干细胞在缺血性心脏病中的应用

骨髓间质干细胞(MSCs)是一种多能造血于细胞,在一定诱导条件下,可分化为多种造血外组织细胞,如骨细胞、软骨细胞、 心肌细胞等,因此,在组织工程方面具有广泛的应用前景。近年来,MSCs在缺血性心脏病中的应用价值已得到证实和肯定,从而为 缺血性心脏病的治疗带来了新的契机。本文就骨髓间质干细胞在缺血性心脏病中的应用进行了回顾和展望。     

Manipulation of pancreatic stem cells for cell replacement therapy

The demonstration of the existence of tissue-specific adult stem cells has had a great impact on our understanding of stem cell biology and its application in clinical medicine. Their existence has revolutionized the implications for the treatment of many degenerative diseases characterized by either the loss or malfunction of discrete cell types. However, successful exploitation of this opportunity requires that we have sufficient know-how of stem cell manipulation. Because stem cells are the founders of virtually all tissues during embryonic development, we believe that understanding the cellular and molecular mechanisms of embryogenesis and organogenesis will ultimately serve as a platform to identify factors and conditions that regulate stem cell behavior. Discovery of stem cell regulatory factors will create potential pharmaceutical opportunities for treatment of degenerative diseases, as well as providing critical knowledge of the processes by which stem cells can be expanded in vitro, differentiated, and matured into desired functional cells for implantation into humans. A well-characterized example of this is the hematopoietic system where the discovery of erythropoietin (EPO) and granulocyte-colony stimulating factor (G-CSF), which regulate hematopoietic progenitor cell behavior, have provided significant clinical success in disease treatment as well as providing important insights into hematopoiesis. In contrast, little is known about the identity of pancreatic stem cells, the focus of this review. Recent reports of the potential existence of pancreatic stem cells and their utility in rescuing the diabetic state now raise the same possibilities of generating insulin-producing beta cells as well as other cell types of the pancreatic islet from a stem cell. In this review, we will focus on the potential of these new developments and how our understanding of pancreas development can help design strategies and approaches by which a cell replacement therapy can be implemented for the treatment of insulin-dependent diabetes which is manifested by the loss of beta cells in the pancreas.     

Resident cardiac stem cells

The search for sources of stem/progenitor cells the use of which has a potential to affect course of ischemic heart disease and chronic heart failure is conducted nowadays in many countries. Resident cardiac stem cells (CSC) were revealed during recent years on the basis of expression of c-kit, sca-1, MDR1, and islet-1 markers. In vitro experiments demonstrated possibility of their differentiation into cardiomyocytes, smooth muscle cell and endothelial cells. Introduction of CSC in injured myocardium in animals facilitated its partial repair and short term improvement of cardiac function. This holds promise for the use of these cells in the future. In the review we have attempted to summarize literature data on resident CSC and their application for the treatment of heart diseases.     

ALDH高活性干细胞治疗缺血性疾病的研究进展

ALDH高活性细胞（ALDH bright stem cells,ALDHbr）是以细胞质中的乙醛脱氢酶活性为基础筛选获得的含有各种干细胞和祖细胞的细胞群,ALDHbr细胞作为多种干细胞的混合体,具有各种干细胞特性,ALDHbr细胞能够通过自分泌和旁分泌机制产生促血管新生因子,或者转移到损伤部位直接分化成成熟细胞。与CD34＋、CD133＋等这些根据细胞表型筛选的干细胞相比,ALDHbr细胞改善灌注,促进血管新生,增加血管密度的效果更显著。近期,一些自体的或异体来源的ALDHbr细胞群已经被作为一种治疗手段在临床试验中应用于修复组织缺血损伤。本文重点综述了ALDHbr细胞的定义与起源,筛选方法,促进血管新生的作用和机制以及在缺血性心脏病和外周缺血性疾病中的应用。     

内皮前体细胞移植:冠心病治疗的新策略

干细胞研究的进展和基因治疗技术在心血管的应用为缺血性心脏病的治疗提供了新策略。基因修饰后内皮前体细胞移植既补充了功能不良且数量不足的内皮前体细胞又诱导并促进了局部新血管的生成 ,展示了美好的临床应用前景。本文回顾了近几年来缺血性心脏病治疗的新概念 ,重点介绍了国外内皮前体细胞及其基因修饰应用的新进展 ,并对存在的问题和应用前景分别进行了讨论和展望     

An introduction to induced pluripotent stem cells

Recent landmark studies show that it is now possible to convert somatic cells, such as skin fibroblasts and B lymphocytes, into pluripotent stem cells that closely resemble embryonic stem cells. These induced pluripotent stem (iPS) cells can be generated without using human embryos or oocytes, thus bypassing some of the ethical issues that have limited the use of human embryonic stems (hES) cells. Additionally, they can be derived from the patient to be treated, thereby overcoming problems of immunological rejection associated with the use of allogeneic hES cell derived progenitors. Whilst these patient‐specific iPS cells have great clinical potential, their immediate utility is likely to be in drug screening and for understanding the disease process. This review discusses the promise of iPS cells as well as the challenges to their use in the clinic.