脐带间充质干细胞与再生障碍性贫血

再生障碍性贫血(aplastic anemia,AA)是由于物理、化学、生物或不明因素作用使骨髓造血干细胞和骨髓微环境严重受损,造成骨髓造血功能降低或衰竭,以全血细胞减少为主要表现的一组综合征。间充质干细胞(MSC)是属于中胚层的一类多能干细胞,主要存在于结缔组织和器官间质中。不仅具有多向分化潜能,还有多种免疫调节作用。许多研究表明MSCs抑制同种异体效应T淋巴细胞增殖,还能下调T淋巴细胞表面的活化分子CD25、CD38、CD69的表达。MSCs对DCs的分化、成熟和活化具有抑制作用,改变DCs的细胞因子分泌,使成熟的DCl分泌TNF-a减少,DC2分泌IL-10增加,从而抑制T淋巴细胞增殖。MSCs能够抑制IL-2和IL-15介导的NK细胞增殖,使IL-2刺激NK细胞分泌的IFN-y减少。通过这些机制来干预再生障碍性贫血,同时研究发现MSCs免疫原性较低。尤其脐带MSC,因为其独特优势,目前已经成为干细胞干预治疗AA的研究热点。     

编委推荐

<正>Cell|造血干细胞微环境的形成和维持具有不同的表观调控机制造血干细胞具有自我更新和多谱系分化的潜能,可以维持血液系统稳态。在生理状态下,成体造血干细胞位于骨髓微环境中。间充质细胞(MSC)是骨髓造血干细胞微环境的关键组成成分,其中LepR⁺ MSC通过分泌造血干细胞维持因子,如SCF和CXCL12,支持造血干细胞的功能。     

间充质干细胞体外调控骨髓造血前体细胞向单核系分化

研究间充质干细胞(MSC)能否在体外调控造血。体外分离培养人骨髓来源的MSC,RT-PCR检测其造血生长因子的表达,并以其为饲养层细胞,接种骨髓单个核细胞(MNC),观察生长情况,并通过形态学观察和流式细胞术分析,鉴定细胞来源和分化方向。结果显示,MSC构成性表达SCF、Flt3L和M-CSF,不表达C-CSF和GM-CSF,在骨髓MNC和MSC共培养体系中,大约2周左右可以看到大量的圆形细胞粘附在梭型MSC上生长,细胞胞体为圆形,胞浆较丰富,胞核为圆形、半月型或肾型,部分细胞呈典型的单核细胞形态,流式细胞术分析该类细胞表达CDl4,不表达CDl5、CD41、glycophorin A、CD5和CDl9。表明不需要添加外源性造血生长因子,间充质干细胞能在体外调控骨髓造血前体细胞向单核系分化,其定向分化可能与MSC分泌造血生长因子及MSC与造血细胞间相互作用有关。     

问充质干细胞体外调控骨髓造血前体细胞向单核系分化

研究间充质干细胞(MSC)能否在体外调控造血.体外分离培养人骨髓来源的MSC,RT-PCR检测其造血生长因子的表达,并以其为饲养层细胞,接种骨髓单个核细胞(MNC),观察生长情况,并通过形态学观察和流式细胞术分析,鉴定细胞来源和分化方向.结果显示,MSC构成性表达SCF、Flt3L和M-CSF,不表达G-CSF和GM-CSF,在骨髓MNC和MSC共培养体系中,大约2周左右可以看到大量的圆形细胞粘附在梭型MSC上生长,细胞胞体为圆形,胞浆较丰富,胞核为圆形、半月型或肾型,部分细胞呈典型的单核细胞形态,流式细胞术分析该类细胞表达CD14,不表达CD15、CD41、glycophorin A、CD5和CD19.表明不需要添加外源性造血生长因子,间充质干细胞能在体外调控骨髓造血前体细胞向单核系分化,其定向分化可能与MSC分泌造血生长因子及MSC与造血细胞间相互作用有关.     

IL-33转基因小鼠骨髓造血干／祖细胞向髓系细胞分化的能力增强

目的：利用IL-33转基因小鼠研究IL-33对造血干/祖细胞的增殖和分化影响。方法利用流式细胞仪分析IL-33转基因小鼠及同窝野生对照小鼠的外周血、脾脏、骨髓细胞的免疫表型及造血干细胞分化不同阶段细胞的数量变化;利用体外成克隆实验和细胞周期分析研究IL-33对于造血干细胞增殖能力的影响。结果与野生型小鼠相比,IL-33转基因小鼠B细胞和T细胞在外周血中都明显降低,粒细胞在外周血和骨髓中都有明显增加;IL-33转基因小鼠的骨髓造血干细胞和多能祖细胞数量减少,共同淋系祖细胞数量减少,共同髓系祖细胞和粒单系祖细胞数量增加;IL-33转基因小鼠的造血干细胞处于S-G2-M的细胞增多;体外单克隆实验发现IL-33转基因小鼠造血干细胞形成的集落数增加。结论 IL-33转基因小鼠造血干细胞增殖能力增强,更易向髓系细胞分化。     

间充质干细胞对造血干/祖细胞分化为巨核细胞的影响

目的:探讨间充质干细胞(MSC)共培养对体外诱导脐带血单个核细胞来源的造血干/祖细胞生成巨核细胞的影响。方法:分离得到骨髓和脐带2种来源的MSC,并对它们进行表面标志和多向分化能力的鉴定,同时通过实时定量PCR及对RT-PCR产物的电泳分析,对比相同培养代数下2种MSC表达造血因子的情况;用梯度离心法分离得到单个核细胞,通过直接接触或Trans-well分隔的方式分别与MSC共培养,观察细胞增殖情况,并检测巨核系特异性的表面标志和相关基因的表达。结果:骨髓和脐带来源的MSC均分泌对巨核细胞增殖分化有促进作用的造血因子,与造血干/祖细胞直接共培养,对于巨核细胞的增殖有明显的促进作用,分化效果不明显;在非接触共培养的条件下,对巨核细胞的增殖及分化都产生促进作用,且骨髓来源的MSC较脐带来源的MSC效果更加明显。结论:MSC与脐带血造血干/祖细胞非接触培养,对其向巨核分化和增殖的促进作用明显,本实验所用的骨髓来源MSC促分化效果更好。本研究为今后进一步优化巨核系诱导分化体系奠定了基础,并对未来体外大规模制备巨核系祖细胞应用于临床治疗有一定的指导作用。     

共表达PDX1和BTC间充质干细胞对转分化胰岛素分泌细胞的影响

该文通过Tet调控下共表达PDX1与BTC的骨髓间充质干细胞系(PDX1~+BTC~+MSCs),探讨PDX1和BTC共表达对骨髓间充质干细胞分化为胰岛素分泌细胞(IPCs)的效率及成熟度的影响。采用两步法对PDX1~+BTC~+MSCs细胞系诱导分化成IPCs,第一步Dox诱导7天检测到Nestin、CK19表达;第二步再诱导7天后形成DTZ染色阳性的胰岛样结构,Ngn3、Nkx6.1 mRNA水平和PDX1、Insulin、Glucagon的蛋白表达阳性。分化后的IPCs在葡萄糖刺激下能产生胰岛素和C肽,但仍不能达到正常胰岛水平。提示利用Tet-On体系调控PDX1和BTC共表达对骨髓间充质干细胞进行修饰,能有效诱导骨髓间充质干细胞分化为胰岛素分泌细胞,但分化成熟度仍然与天然胰岛细胞功能存在差距。     

间充质干细胞免疫抑制作用及其在移植免疫中应用的研究进展

间充质干细胞(MSC)是一类具有自我更新、增殖和多向分化潜能的干细胞,具有向内、中、外3个胚层包括肌腱、韧带、肝细胞、心肌细胞和骨髓基质细胞等分化、发育的潜能。有研究表明,MSC具有较低的免疫原性,它可以通过与免疫细胞直接接触和分泌细胞因子等机制发挥免疫调节作用,从而成为移植免疫领域的研究热点,本文就MSC的生物学特性、免疫抑制作用及在移植免疫中的应用做一综述。     

巨核细胞生成调控相关细胞因子及其作用研究进展

造血干细胞分化生成巨核细胞是一个十分复杂的过程,包括造血干细胞动员及其向巨核系祖细胞分化,巨核系祖细胞增殖、分化生成未成熟巨核细胞,巨核细胞的成熟和血小板释放等过程。研究发现,造血干细胞动员及其向各系细胞分化的大部分过程都在一种称为"龛"的结构中进行,多种龛内信号分子参与了造血干细胞的动员和分化调控。该文对造血干细胞龛内参与造血干细胞动员和分化生成巨核细胞的几种重要细胞因子及其调控作用进行综述。     

生长因子诱导人脐带/胎盘间充质干细胞定向分化

近年来,间充质干细胞(mesenchymal stem cell,MSC)已成为干细胞领域的研究热点,其不仅支持造血系统,还可在特定的培养条件下向多种组织细胞分化。人脐带和胎盘来源的MSC取材容易,较骨髓间充质干细胞有更广泛的应用前景。本文就含有特定生长因子的培养基诱导人脐带MSC和人胎盘MSC定向分化的研究进展作一简要的综述。     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.     

肝癌中HBV和HCV基因和抗原的分布及意义

采用原位分子杂交方法检测HCV RNA及HBV X基因;采用免疫组织化学方法研究HCV核心抗原,非结构区C33c抗原及HBxAg在肝细胞肝癌中的定位及分布.结果表明(1)HCV RNA、HBV X基因在肝细胞肝癌组织检出率分别为40%(55/136)和82%(112/136).HCV RNA定位于癌细胞的胞浆内,阳性细胞呈散在、灶状及弥漫分布三种形式;HBV X基因在肝癌细胞中的分布呈胞浆型、核型及核浆型,阳性细胞也呈上述三种分布形式;(2)HCV C33c抗原、核心抗原在肝细胞肝癌中的阳性率为81%(133/164)及86%(141/164).C33c抗原定位于癌细胞及肝细胞的胞浆内;核心抗原既定位于癌细胞核中,又可定位于胞浆中.C33c抗原阳性细胞以灶状分布为主;而核心抗原阳性细     

Selection with two alleles and complete dominance

For a plant selection model with frequency-independent viabilities, fertilities and selfing rates, it is shown that apart from global fixation, for certain parameter combinations a protected polymorphism and facultative fixation (either allele may become fixed according to initial frequencies) may both occur. Facultative fixation requires different selling rates for the dominant and recessive type. Protection of the polymorphism requires resource allocation for male and female function. In this connection the problem of purely genetically caused population extinction is discussed.
For general frequency dependence and regular segregation, the chances for establishment of a completely recessive gene are compared to those of a completely dominant gene. It is proven that the process of establishment of the recessive gene, despite a fitness advantage, may be considerably endangered by drift effects if random mating prevails. The recessive gene may reach the same effectivity in establishment as a dominant gene, only if the recessive homozygote mates exclusively with its own type during the period of establishment.