文献检索作业3生物技术112 邹炜球 11114040235.docx

1、文献检索作业3 生物技术112 邹炜球 11114040235生物技术11-2 邹炜球 11114040235检索主题：人类胚胎干细胞的新潜力一、我感兴趣的原因：由于以下几个原因，胚胎干细胞的研究使人感到激动。首先是它们拥有类似胚胎的全能分化性，可以从单个的受精卵发育成完整的个体，能够给我们解释完整的发育体系，而成体个体来源的多能干细胞就不可能。同时，极早期的胚胎发育均可追溯到ES细胞，而不可能是成熟个体来源的多能干细胞。ES细胞也是唯一不死的细胞，能够非限定地分化，是细胞的源头。ES细胞天生就是全能的，这就是问题的关键，换言之，他们能制造机体需要的全部细胞。最后，ES细胞是遗传操作的最早期细

2、胞。因此，尽管争论集中在治疗方面，但也许ES细胞最伟大的用途是作为科学研究的工具。人胚胎干细胞的分离及体外培养的成功，将给人类带来医学革命。如果科学家最终能够成功诱导和调控体外培养的胚胎干细胞正常的分化，这一技术将对基础研究和临床应用产生巨大的影响，有可能在以下领域发挥作用：体外研究人胚胎的发生发育，非正常发育（通过改变细胞系的靶基因），新人类基因的发现，药物筛选和致畸实验，以及作为组织移植、细胞治疗和基因治疗的细胞源等。人胚胎干细胞提供了在细胞和分子水平上研究人体发育过程中的极早期事件的良好材料和方法，这种研究不会引起与胚胎实验相关的伦理问题。采用基因芯片等技术，比较胚胎干细胞以及不同发育阶

3、段的干细胞和分化细胞的基因转录和表达，可以确定胚胎发育及细胞分化的分子机制，发现新的人类基因。结合基因打靶技术，可发现不同基因在生命活动中的功能等。另一个令人兴奋的应用在于新药的发现及筛选。胚胎干细胞提供了新药的药理、药效、毒理及药代等研究的细胞水平的研究手段，大大减少了药物实验所需动物的数量。上述实验使用的细胞系或来自其他种属的细胞系，很多时候并不能真正代表正常的人体细胞对药物的反应。胚胎干细胞还可用来研究人类疾病的发生机制和发展过程，以便找到有效和持久的治疗方法。二、检索方法：打开http:/www.sciencemag.org/ 进入science 网站 在检索栏输入 All scien

4、ce journals Embryonic stem cell research and application 搜索结果： 1、New Potential for Human Embryonic Stem Cells下图为检索文献结果：原文：Science 6 November 1998: Vol. 282 no. 5391 pp. 1061-1062 DOI: 10.1126/science.282.5391.1061 PerspectiveCELL BIOLOGYNew Potential for Human Embryonic Stem Cells1. John Gearhart*+

5、Author Affiliations1. The author is in the Department of Gynecology and Obstetrics, Johns Hopkins Medicine, Baltimore, MD 21287, USA. E-mail: gearhartjhmi.eduPluripotential stem cells, present in the early stages of embryo development, can generate all of the cell types in a fetus and in the adult a

6、nd are capable of self-renewal. A renewable, tissue culture source of human cells capable of differentiating into a wide variety of cell types would have broad applications in basic research and transplantation therapies. A major step in realizing this goal has now been taken with the demonstration

7、that human embryonic stem cells can be grown in culture. These stem cells have been derived in culture from two embryonic tissues: inner cell masses of blastocysts (those cells within the conceptus that form the embryo proper) and primordial germ cells. Embryonic stem (ES) cells were first derived f

8、rom the inner cell masses of mouse blastocysts in the early 1980s (1, 2). More recently, primordial germ cell cultures were found to give rise to cells with characteristics of ES cells and were designated EG (embryonic germ) to distinguish their tissue of origin (3, 4). ES and EG cells have now been

9、 derived from embryos of other mammals, including primates (510). Now on page 1145 of this issue, Thomson et al. (11) report the derivation of ES cell lines from human blastocysts. Pluripotential stem cells, primarily ES cells, have been used extensively in studies of embryogenesis, gene function, a

10、nd development in the mouse (11). ES and EG cells transferred to a mouse blastocyst can contribute substantially to all differentiated cell types in the fetus, including the germ line. Consequently, gene targeting within ES cells has enabled both whole-animal studies of gene function and the product

11、ion of mouse models of human genetic diseases and abnormalities. ES and EG cells have also been used to study the differentiation of various cell types and tissues in vitro, such as neural cells (1216), hematopoietic lineages (1719), and cardiomyocytes (20). ES-derived cells have been successfully t

12、ransplanted into fetal and adult mice, where they have demonstrated morphological and functional integration (1923). Thomsons group at the Wisconsin Regional Primate Research Center in Madison, in collaboration with the Departments of Obstetrics and Gynecology at the Rambam Medical Center in Haifa,

13、Israel, and the University of Wisconsin, reports the derivation of five independent cell lines from the inner cell masses of 14 blastocysts (11). The ES cell lines were continuously cultured for 5 to 6 months and expressed high levels of telomerase activity, characteristic of cells with high replica

14、tive life-span. The cell lines had normal karyotypes (two male and three female) and expressed cell surface markers characteristic of ES cells. Four cell lines tested produced teratomas when grown in immunocompromised mice. Histology of the tumors revealed differentiated cells derived from all three

15、 embryonic germ layers (ectoderm, mesoderm, and definitive endoderm)a result consistent with pluripotency. This report of the derivation of ES cells from human blastocysts represents a major technical achievement with great importance for human biology. Although ES cells have been derived from sever

16、al mammalian species, other species have proved refractory in yielding ES cells. It was, therefore, not a foregone conclusion that ES cells could be derived from human embryos. Earlier publications from the Thomson group reporting the derivation of ES cells from nonhuman primates increased the expec

17、tation that such cells could be derived from human blastocysts. In a related report, it now appears that human embryos are also amenable to EG cell derivation from primordial germ cells (24). The derivation of human ES cells now raises a whole new set of expectations. On the basis of the use and stu

18、dy of mouse ES cells, the research and clinical potential for human ES cells is enormous. They will be important for in vitro studies of normal human embryogenesis, abnormal development (through the generation of cell lines with targeted gene alterations and engineered chromosomes), human gene disco

19、very, and drug and teratogen testing and as a renewable source of cells for tissue transplantation, cell replacement, and gene therapies. These latter applications could eventually preclude the direct use of fetal tissue in transplantation therapies. It is exciting to speculate on how human ES lines

20、 could be used in tissue transplantation therapies (see figure) (25). Obvious clinical targets would include neurodegenerative disorders, diabetes, spinal cord injury, and hematopoietic repopulation. In addition to possibly providing large numbers of pure populations of cells for transplantation, ES

21、 cells would also lend themselves to several strategies for the prevention of immunological tissue rejection after transplantation, including (i) banking of multiple ES cell lines representing a spectrum of major histocompatibility complex (MHC) alleles to serve as a source for MHC matching; (ii) cr

22、eation of universal donor lines, in which the MHC genes could be genetically altered so rejection would not occur, an approach that has been tried with moderate success in the mouse; (iii) customization of ES cells through transgenesis and gene targeting so that a potential recipients MHC genes are

23、introduced into ES cells through homologous recombination; and (iv) production of ES lines containing the genome of the prospective recipient. Blastocysts obtained through nuclear transfers would be used to generate ES cells, which then could be differentiated to specific lineages for transfer to th

24、e nuclear donor (26). Because EG cells have been shown to reprogram adult nuclei (27) after cell hybrid formation, it may eventually be possible to do nuclear transfers into pluripotent stem cells, which could then be expanded and differentiated. Embryonic stem cell differentiation.Possible applicat

25、ions of ES cells to transplantation therapy.To realize the full potential of human pluripotent stem cells, challenging research lies ahead and several practical issues must be resolved. The conditions necessary to derive human ES cells efficiently and reliably must be defined. How did the Thomson gr

26、oup succeed when, on the surface, their protocol is so similar to that of other investigators? Their previous experience with nonhuman primate ES cell derivation was certainly critical for this success. Thomson et al. (11) report that of 14 inner cell masses placed in culture, five ES cell lines wer

27、e established. This result is excellent, but could it be better? Are there ways of assaying blastocysts for their potential of yielding ES cells? As in the mouse, are there predisposing genes for this property? Are there other extrinsic or intrinsic factors that may lead to a greater success rate? T

28、he conditions for directed, lineage-restricted differentiation of ES cells must be defined. Studies to date on ES cell differentiation in vitro rely primarily on the selection and enrichment of specific lineages from the many that may be present when cell differentiation is induced. Also, strategies

29、 must be developed to obtain the large numbers of pure populations of cells that would be required for engraftments. In the short term, feeder cell-independent lines will have to be derived and methods for complete cell disaggregation developed. It must also be determined if the cells are amenable t

30、o transfections, enabling selection and gene-targeting strategies. Reports on the isolation of human pluripotent stem cells will no doubt catch the public eye, and there will be expressions of concern, rekindling the debate on human embryo research. The debate will encompass the source of the cells,

31、 human cloning potential, and the possibilities of germ line modifications. Four years ago, the Human Embryo Research Panels report to the director of the National Institutes of Health (NIH) concluded that research deriving ES cells is acceptable as long as embryos are not created expressly for rese

32、arch purposes. Several issues will have to be resolved to permit the appropriate exploitation of the uniqueness and potential of these cells. Currently, as broadly written, U.S. federal law bans the use of federal funds for the derivation of these cells Public Law 10578, Section 513(a). To date, res

33、earch in this area has been sponsored through private and corporate funding, with hospital and academic institutional internal review board approval and informed patient consent. It is not clear whether NIH funding necessary to realize the biomedical potential of the cells will be available to support studi