干細(xì)胞的研究課件

1、干細(xì)胞的研究陳 朗Definition干細(xì)胞(stem cell)是一類具有自我更新和分化潛能的細(xì)胞。 Classification單能干細(xì)胞multipotent stem cell： 肝細(xì)胞（出生后肝細(xì)胞的再生）多能干細(xì)胞pluripotent stem cell： 造血干細(xì)胞全能干細(xì)胞Totipotent stem cell： ES細(xì)胞Stem cell來 源分化潛能胚胎干細(xì)胞成體干細(xì)胞Embryonic Stem cell胚胎干細(xì)胞 當(dāng)受精卵分裂發(fā)育成囊胚時(shí)，內(nèi)層細(xì)胞團(tuán)（Inner Cell Mass）的細(xì)胞即為胚胎干細(xì)胞（Embryonic Stem cell, ES細(xì)胞）。Jame

2、s A. Thomson, Wisconsin University, 1998 John D. Gearhart, Johns Hopkins, 1998Adult stem cells成體干細(xì)胞 成體干細(xì)胞是在成體組織內(nèi)具有自我更新能力及能分化產(chǎn)生一種或一種以上子代組織細(xì)胞的未成熟細(xì)胞。 成年動(dòng)物的許多組織和器官，比如表皮和造血系統(tǒng)，具有修復(fù)和再生的能力。成體干細(xì)胞在其中起著關(guān)鍵的作用。在特定條件下，成體干細(xì)胞或者產(chǎn)生新的干細(xì)胞，或者按一定的程序分化，形成新的功能細(xì)胞，從而使組織和器官保持生長和衰退的動(dòng)態(tài)平衡。How many kinds of adult stem cells exist

3、, and in which tissues do they exist? What are the sources of adult stem cells in the body? Are they leftover embryonic stem cells, or do they arise in some other way? Why do they remain in an undifferentiated state when all the cells around them have differentiated? Do adult stem cells normally exh

4、ibit plasticity, or do they only transdifferentiate when scientists manipulate them experimentally? What are the signals that regulate the proliferation and differentiation of stem cells that demonstrate plasticity? Is it possible to manipulate adult stem cells to enhance their proliferation so that

5、 sufficient tissue for transplants can be produced? Does a single type of stem cell existpossibly in the bone marrow or circulating in the bloodthat can generate the cells of any organ or tissue? What are the factors that stimulate stem cells to relocate to sites of injury or damage? Characteristics

6、多能性或全能性 干細(xì)胞具有分化為多種細(xì)胞類型的潛能，但不同干細(xì)胞的分化潛能有所不同。Such as: ES細(xì)胞具有全能性; HSC具有多能性Characteristics自我更新能力( self-renewing) 干細(xì)胞一旦形成，在機(jī)體終生都具有自我更新能力，它可通過不對稱分裂進(jìn)行自我更新和產(chǎn)生新的祖細(xì)胞。FateRemain quiescent Undergo apoptosis Undergo symmetric cell divisions to self-renew Undergo terminal differentiation Undergo asymmetric cell di

7、visions to generate differentiated progeny as well as maintain a pool of stem cells Transit to another kind of stem cell or transdifferentiate to acquire a distinct set of properties Regulate the development of SCs干細(xì)胞的調(diào)控 是指給出適當(dāng)?shù)囊蜃訔l件,對干細(xì)胞的增殖和分化進(jìn)行調(diào)控，使之向指定的方向發(fā)展。Regulate the development of SCs1. 內(nèi)源性調(diào)控 干

8、細(xì)胞自身有許多調(diào)控因子可對外界信號起反應(yīng)從而調(diào)節(jié)其增殖和分化，包括調(diào)節(jié)細(xì)胞不對稱分裂的蛋白，控制基因表達(dá)的核因子等。另外，干細(xì)胞在終末分化之前所進(jìn)行的分裂次數(shù)也受到細(xì)胞內(nèi)調(diào)控因子的制約。 Regulate the development of SCs1）細(xì)胞內(nèi)蛋白 細(xì)胞的結(jié)構(gòu)蛋白，特別是細(xì)胞骨架成分對干細(xì)胞的發(fā)育非常重要。收縮體與紡錘體的結(jié)合決定了干細(xì)胞分裂的部位，從而把維持干細(xì)胞性狀所必需的成分保留在子代干細(xì)胞中。2）轉(zhuǎn)錄因子 在脊椎動(dòng)物，轉(zhuǎn)錄因子對干細(xì)胞分化的調(diào)節(jié)非常重要。比如在胚胎干細(xì)胞的發(fā)生中，轉(zhuǎn)錄因子Oct4是必需的。Oct4是一種哺乳動(dòng)物早期胚胎細(xì)胞表達(dá)的轉(zhuǎn)錄因子，它誘導(dǎo)表達(dá)的靶基

9、因產(chǎn)物是FGF-4等生長因子，能夠通過生長因子的旁分泌作用調(diào)節(jié)干細(xì)胞以及周圍滋養(yǎng)層的進(jìn)一步分化。Regulate the development of SCs2. 外源性調(diào)控 除內(nèi)源性調(diào)控外，干細(xì)胞的分化還可受到其周圍組織及細(xì)胞外基質(zhì)等外源性因素的影響。Regulate the development of SCs1）細(xì)胞因子 間質(zhì)細(xì)胞可分泌許多因子，維持干細(xì)胞的增殖、分化和存活。 有兩類因子在不同組織甚至不同種屬中都發(fā)揮重要作用，它們是TGF家族和Wnt信號通路。比如TGF家族中至少有兩個(gè)成員能夠調(diào)節(jié)神經(jīng)嵴干細(xì)胞的分化。Wnt的作用機(jī)制是通過阻止-Catenin分解從而激活 Tcf/Lef介

10、導(dǎo)的轉(zhuǎn)錄，促進(jìn)干細(xì)胞的分化。Applications干細(xì)胞在生命科學(xué)的各個(gè)領(lǐng)域都有著重要而深遠(yuǎn)的影響，如克隆動(dòng)物、轉(zhuǎn)基因動(dòng)物的生產(chǎn)、細(xì)胞組織和器官的修復(fù)和移植治療、組織工程上有著廣闊的應(yīng)用前景。Applications2. 克隆動(dòng)物及轉(zhuǎn)基因動(dòng)物的生產(chǎn) 自綿羊“多莉”問世至今，體細(xì)胞克隆動(dòng)物多有成功的報(bào)道。但體細(xì)胞克隆動(dòng)物有著無法克服的弊端，即成功率低和容易早衰。轉(zhuǎn)基因動(dòng)物是利用受精卵或ES細(xì)胞作為載體，通過注射目的基因，生產(chǎn)出帶有目的基因的動(dòng)物。Wilmut et al. Dolly sheep, 1996, Nature, 385: 810 Applications3. 轉(zhuǎn)基因干細(xì)胞基因治療

11、 轉(zhuǎn)基因細(xì)胞治療常用的基因轉(zhuǎn)移靶細(xì)胞多為淋巴細(xì)胞、成纖維細(xì)胞等。細(xì)胞存活時(shí)間有限，在治療過程中需要反復(fù)輸注，治療繁瑣。轉(zhuǎn)基因干細(xì)胞技術(shù)建立解決了轉(zhuǎn)基因細(xì)胞存活問題，成為轉(zhuǎn)基因細(xì)胞治療重要的方向。 Applications4. 生物學(xué)和基礎(chǔ)醫(yī)學(xué)研究人類發(fā)育生物學(xué)基因組研究(基因組和干細(xì)胞的研究進(jìn)展評為2000國際十大科技成果)藥物開發(fā)和毒性測試腫瘤發(fā)病學(xué)：腫瘤干細(xì)胞Researches on SCsDr. Ira Black University of Medicine and Dentistry of New Jersey The stem cells, treated with growth

12、 factors and antioxidants in tissue culture experiments, quickly divided into two cells - another stem cell and a nerve cell. Black and his colleagues were able to turn 80 percent of the bone marrow cells taken from rats and humans into nerve cells. Macklis HMSInduce stem cells deep in the cerebral

13、cortex of adult mice to replace damaged neurons. The new neurons grew from already present immature precursor cells into fully formed, connected, and mature replacements. 從成年小白鼠未發(fā)育的腦干細(xì)胞轉(zhuǎn)變?yōu)榧∪饧?xì)胞他們也用成年人志愿者的神經(jīng)干細(xì)胞實(shí)現(xiàn)了同樣的工作Angelo Vescovi, Giulio Cossu, the Institute for Stem Cell Research in Milan 2000 Res

14、earches on SCsResearches on SCs 在受精卵第三次分裂的八細(xì)胞階段，從其中取出一個(gè)胚細(xì)胞(blastomere)，加以培養(yǎng)形成新的胚胎干細(xì)胞株;另一方面，剩下七個(gè)細(xì)胞的受精卵仍可繼續(xù)發(fā)育，植入母體子宮內(nèi)著床，產(chǎn)下健康的寶寶。 Robert Lanza率領(lǐng)的研究團(tuán)隊(duì)使用此法，已於2005年培養(yǎng)形成新的小鼠胚胎干細(xì)胞株， 并於2006年培養(yǎng)出人類胚胎干細(xì)胞株。八細(xì)胞階段Researches on SCs2006年，美國哈佛大學(xué)宣布，學(xué)校將啟動(dòng)用于治療目的的人類胚胎干細(xì)胞克隆研究項(xiàng)目。目旨在尋找糖尿病、運(yùn)動(dòng)神經(jīng)元疾?。ūR格里希?。┖脱翰。ㄧ牋罴?xì)胞貧血病和白血?。┑闹委熮k

15、法。一座總面積為46萬平方米的哈佛干細(xì)胞研究所將于明年破土動(dòng)工。 Researches on SCsGergen: Stem cell research essential to keep U.S. competitive in science 2006年11月2日 Source: Harvard GazetteIsolate a master heart cell 2006年11月23日Researches on SCs胚胎干細(xì)胞疫苗：肺癌、心臟病 。英國Insulin-Producing Cells Generated from HumanEmbryonic Stem Cells Park

16、insons DiseaseVision LossNeurons Grown Researches on SCs英國西倫敦的一對夫婦都攜帶有一種嚴(yán)重的基因缺陷，他們求助基因篩選技術(shù)，兩月前生下一對健康的“設(shè)計(jì)嬰兒”。Researches on SCs日本京都大學(xué) 用現(xiàn)有的胚胎干細(xì)胞和患者自身的體細(xì)胞融合培養(yǎng)一種“萬能細(xì)胞”。由于這種方法只使用體細(xì)胞和現(xiàn)有胚胎干細(xì)胞，因此基本不觸及倫理問題。 Nature technology干細(xì)胞研究產(chǎn)業(yè)化 自從美國科學(xué)雜志1999年和2000年連續(xù)兩次將干細(xì)胞生物學(xué)和干細(xì)胞生物工程評為世界十大科學(xué)成就之首以來，干細(xì)胞（stem cells）領(lǐng)域就持續(xù)成為國內(nèi)

17、外醫(yī)學(xué)和生物學(xué)研究的熱點(diǎn)。預(yù)測數(shù)字顯示，未來20年內(nèi)，干細(xì)胞醫(yī)療市場的全球規(guī)模將迅速增長，2020年將達(dá)到4000億美元。 Stem cells: hype or hope? Tumor-forming potential of ESCs.The potential immunogenicity of the hES cell lines.The ethical and political concerns over the use of embryos for research.Before ES cells may be used in therapyMethods for the dir

18、ected differentiation of ES cells and the selective isolation of pure population of defined cells have to be established. It has to be shown that ES-cell-derived somatic donor cells are not tumorigenic. It has been known for a long time that undifferentiated early embryonal cells are able to give ri

19、se to teratomas or teratocarcinomas when transplanted to extrauterine site. The integration and tissue-specific function of the ES-cell-generated somatic cells after transplantation have to be shown. Another important question to be solved is the immunological incompatibility between ES-cell generat

20、ed donor cells and the specific organism after transplantation. To overcome these problems, the genetic manipulation of histocompatibility genes in donor cells, immunosuppression in the organism after transplantation, or a new strategy which allow the derivation of autologous donor cells for transplantation, called therapeutic cloning, have been discussed.Websits/packages/