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干细胞与再生医学

需要重点看的概念1 embryonic stem cells, ES 胚胎干细胞2 Stem cells 干细胞3 hematopoietic stem cell 造血干细胞4 Neural stem cells (NSCs) 神经干细胞are initially present in a single layer of pseudostratified epithelium spanning the entire distance from the central canal to the external limiting membrane. NSCs continue to proliferate, and are patterned over several days in vivo to generate mature neurons, oligodendrocytes, and astrocytes. 神经干细胞起先呈现为单层假复层上皮,覆盖于整个中央管到外部的限制性膜。

神经干细胞能增殖,并在数天内产生成熟的神经元、星形胶质细胞和少突胶质细胞。

5 plasticity 可塑性一种成体干细胞具有生成另一个组织的特化细胞的能力,即成体干细胞具有一定跨系、甚至跨胚层分化的特性,称其为干细胞的可塑性,也称为成体干细胞的横向分化。

Transdifferentiation (plasticity of stem cell): means the adult stem cell from one embryonic layer can differentiate into cells derives from other layer.6 Human mesenchymal stem cells 人间充质干细胞7.fate mapping 干细胞命运图:在正常环境下受各种稳态因素调节的分化趋势。

这些趋势包括干细胞对机体正常发育活动的参与,以及干细胞对各种生物学危险诸如组织损伤、器官衰老以及疾病的反应。

判断7 There must be stem cells that divide and generate neurons in the adult mammalian brain. (T)在成年的哺乳类动物体内一定有能够分裂并产生神经元得干细胞存在填空8 (adult) stem cells have been identified in the brain, particularly in a region important in memory, known as the hippocampus.研究者已经证实脑中含有成体干细胞,特别是在对记忆尤为重要的海马区9 NEP cells continue to proliferate, and are patterned over several days in vivo to generate mature (neurons) , oligodendrocytes, and astrocytes in a characteristic spatial and temporal pattern.神经上皮干细胞持续增殖,并在数天内被模式化,以特有的时空模式产生成熟的神经元、星形胶质细胞和少突胶质细胞。

问答10 neuronal precursors can be isolated from 神经前体细胞可从哪些部位分离1) the developing human brain, 发育中的人脑2) adult human hippocampus, 成人的海马3) the adult ventricular zone 成人的脑室区11 Plasticity of neural crest stem cells 神经嵴干细胞的可塑性1) contributed to ectodermal, 向外胚层分化2) endodermal, 向内胚层分化3) mesodermal tissue.向中胚层分化12 genome manipulation in ES cells 胚胎干细胞中的染色体组操作手段1) Insertional Mutagenesis基因捕获技术and Gene Trapping,基因捕获技术2 )Targeted Gene Modification,靶向基因修正3 )Chromosome Engineering.染色体工程学13 classify of stem cells 干细胞的分类1)胚胎干细胞embryonic stem cells,2) 胚胎生殖细胞embryonic germ cells,3 )成体干细胞Adult stem cells.14 Stem cell markers coating the surface of every cell in the body are specialized proteins, Called receptors, have the capability of selectively binding or adhering to other “signaling” molecules.体内干细胞表面覆盖标记物,这些多种特异性蛋白形成的标记物被称为受体,受体具有选择性结合或者改变其他信号分子的能力。

1.HSC的新定义:HSC是机体内最独特的体细胞群,具有极其高度的自我更新、多向分化、跨系分化(transdifferentiation)与重建长期造血的潜能,以及损伤后再生的能力;除此之外,还具有广泛的迁移和特异性的归巢(homing)特性,能有限定位于相应的造血微环境(microenvironment)中,并以非增殖状态和缺乏系相关抗原的方式存在。

concept and marker of HSCsBeing the most special somattic population, HSCs are characterized by high ability of self renew, pluripotent differentiation, transdifferentiation, reconstitute hematopoiesis and regeneration after injury. Besides these, HSCs have the property of extensive motility and specific homing. They locate in microenvironment in bone marrow and exist as nonproliferation with few lineage markers.2.HSC的分子标记:CD34,CD133,Sca-1(干细胞抗原1,Ly-6A/E),ABCG2 (ATP-binding cassette superfamily G member 2) 、c-kit、lin3.造血干细胞的来源:骨髓(bone marrow)、外周血(peripheral blood)、脐带血(cord blood)、胎儿造血系统(embryonic hematogenesis system)、胚胎干细胞和胚胎生殖细胞(embryonic stem cell and embryonic germline cell)4.重建造血功能(reconstitution)都是HSC的一个必备的重要特性。

它可以分为两个阶段,即短期或早期(short or early-term)及长期或晚期(long or late-term)造血重建,分别是由HPC和HSC两类细胞完成。

Reconstitution is the property highly required in the defination of HSC. It could be divided into two phages, one is short or early-term reconstitution, and the other is long or late-term reconstitution. The cells complete these twophages are HPC and HSC respectively.5.HSC和HPC的主要区别是,HSC有高度自我更新或自我维持能力,但不能增殖或扩增;HPC则有高度增殖或扩增能力,早期部分地以致晚期全部地丧失自我更新或自我维持能力。

Differences between HSC and HPC: HSC can be self renewed and self sustained, however, can not proliferate or amplify;HPC can highly proliferated or amplified, but they may partly loss at the earlier stage or completely loss at the later stage the ability of self renew or self sustain. As the process of differentiation, HPC will die (apoptosis).6.干细胞的自我更新(self-renew):(1)单个细胞的不对称分裂(individual asymmetric cell division) 产生一个子代干细胞和一个迅速分化为祖细胞的子代细胞。

(2)群体的不对称分裂(populational asymmetric cell division) 干细胞分裂产生均具有成为干细胞和定向祖细胞能力的子代细胞。

7.HSCs生成或维持/增殖过程中必不可少的转录因子1. SCL/tal-1和Lmo22. AML13. GA TA-24. p218.干细胞的分化和多形性观点:(1)造血因子是刺激造血的直接作用。

(2)造血调控的机制是多层次复合网络式的(3)核内调控因子是决定造血的关键因子。

(4)核内调控因子在复合体中发挥作用。

(5)谱系抑制为谱系选择机制之一9.HSCs的可塑性:一种成体干细胞具有生成另一个组织的特化细胞的能力,即成体干细胞具有一定跨系、甚至跨胚层分化的特性,称其为干细胞的可塑性,也称为成体干细胞的横向分化。

Transdifferentiation (plasticity of stem cell): means the adult stem cell from one embryonic layer can differentiate into cells derives from other layer.10.制约发展和改进HSCs使用的方法1.HSCs数量的扩增2.宿主、移植物和病原攻击免疫系统的控制3.对分化环境和发育可塑性的理解11.成血-血管干细胞: 在胚胎发育的早期存在来源于侧板中胚层,具有分化为血细胞和血管内皮细胞双重潜能的细胞,这些细胞在原始和终末造血过程,以及血管发生中发挥作用。

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