细胞与细胞工程.ppt

1、a,1,Cell (JL) phase contrast. (A) Normal HeLa cells; (B) treated with staurosporin to induce apoptosis; or (C) treated with thapsigargin to induce autophagy (Galluzzi et al, 2007). (D) Apoptotic, and (E) necroptotic Jurkat cells (Degterev et al, 2005). (F) Paraptotic 293T cells (Sperandio et al, 200

2、0; copyright (2000) National Academy of Sciences, USA). (G) Necrotic and (H) autophagic iBMK cells (Degenhardt et al, 2006; Mathew et al, 2007). (I) Ras-expressing U251 glioblastoma cells showing macropinosomes (J.H. Overmeyer, A. Kaul, E.E. Johnson (3) 经转基因的克隆哺乳动物，将能为人类提供源源不断的廉价的药品、保健品以及较易被人体接受的移植器

3、官； (4) 科学家将很快地从目前的同种克隆技术推进到异种克隆,即借腹怀胎的新领域,这无疑将大大促进对濒临灭种的哺乳动物的保护工作。,克隆技术将对21世纪产生的重大影响（？）,a,57,第一节 细胞的特征 细胞的基础知识 细胞的生长、分化与死亡 第二节 动物细胞工程 动物细胞培养 单克隆抗体 动物克隆 干细胞工程,a,58,Stem cells are powerful tools in biology and medicine. What can scientists do with these cells to exploit their incredible potential?,Ada

4、pted fromPrinciples of Biologypublished byNature Education.,JAMES KING-HOLMES/SCIENCE PHOTO LIBRARY A mouse embryo is held in place during nuclear transfer. The eggs genetic material has been removed and an adult cell nucleus is injected in its place.,四. 干细胞工程,a,59,Pluripotent: can transform into an

5、y one of the 220 cell types in the human body. Self-renewal: one stem cell can also divide to produce millions more stem cells.,1. What are Stem Cells?,a,60,in nearly all animals, from tiny worms to mice and humans. embryonic stem cells adult stem cells induced pluripotent stem (iPS) cells,2. Types

6、of Stem Cells,a,61,Embyonic Stem Cells VS. Adult Stem Cells,Stem Cells: Flexible friends Nature483,S22S26,a,62,In the past decade, scientists have also learned to make stem cells from regular mature, differentiated cells. These cells are called induced pluripotent stem cells because scientists force

7、 them to become pluripotent even after they have reached a differentiated state. By turning up the expression of just a few genes, scientists can force a skin cell, for example, to retrace its developmental pathway backwards all the way to a flexible pluripotent state.,Induced Pluripotent Stem Cells

8、,a,63,3. Medical Applications,Stem cells can teach us about the biology of pluripotent cells, how the human body develops, and what happens during disease. They are also a tool for developing safer ways to design and test new medications. they are the basis for regenerative medicine, using stem cell

9、s to repair damaged tissue. ,a,64,The discoveries of Gurdon and Yamanaka have shown that specialised cells can turn back the developmental clock under certain circumstances. Although their genome undergoes modifications during development, these modifications are not irreversible. We have obtained a

10、 new view of the development of cells and organisms. Research during recent years has shown that iPS cells can give rise to all the different cell types of the body. These discoveries have also provided new tools for scientists around the world and led to remarkable progress in many areas of medicin

11、e. iPS cells can also be prepared from human cells. For instance, skin cells can be obtained from patients with various diseases, reprogrammed, and examined in the laboratory to determine how they differ from cells of healthy individuals. Such cells constitute invaluable tools for understanding dise

12、ase mechanisms and so provide new opportunities to develop medical therapies.,From surprising discovery to medical use,皮肤细胞,iPS,神经细胞,心肌细胞,肝细胞,精子、卵子,a,65,Why is a therapeutic cloning approach important?,By growing new body parts from existing ones from the same person we can avoid transplant rejectio

13、n problems. By using cells re-engineered or “cloned” from ourselves we can become our own transplant source - similar to banking blood for ourselves before a surgical operation.,a,66,People in the US affected by diseases that may be helped by stem cell research,ConditionNumber of Persons Affected Ca

14、rdiovascular diseases 58 Million Autoimmune diseases 30 Million Diabetes16 Million Osteoporosis10 Million Cancer8.2 Million Alzheimers disease4 Million Parkinsons disease1.5 Million Burns (severe) 0.3 Million Spinal cord injuries0.25 Million Birth defects150,000 (per year) Total 128.4 Million - Data

15、 from the Patients Coalition for Urgent Research, Washington, DC (according to Perry, Ref. 267).,a,67,NATURE|NEWS Chinas stem-cell rules go unheeded Health ministrys attempt at regulation has had little effect. Nature484,149150(12 April 2012),Its boom time for firms selling stem-cell treatments, suc

16、h as those derived from umbilical blood. LIU HAIFENG/XINHUA PRESS/CORBIS,a,68,NATURE|NEWS Stem-cell therapy takes off in Texas A boom in unproven procedures is worrying scientists. Nature483,1314(01 March 2012),Celltex hosts the largest stem-cell bank in the United States. TYLER RUDICK,a,69,4. Devel

17、opment of the Stem Cell technique,Source: ,a,70,Where are the Stem Cells?,自然胚胎 克隆人胚胎-核移植/混种胚胎-核移植 体细胞诱导多能干细胞 (体细胞转分化),a,71,In 1868, German biologist Ernst Haeckel first used the term stem cell to describe a zygote. Researchers have been working with mouse embryonic stem cells since 1981. the field t

18、ook off in 1998, when researchers isolated human embryonic stem cells for the first time. （最早的人类多能干细胞是从体外受精的临床病例中得来的多余胚泡。这个里程碑式的事件是James Thomson领导的University of Wisconsin, Madison的实验室在1998年的成果。 ）,3.1 Isolation and culture of Stem Cells,a,72,3.2 Objections to Stem Cell Reasearch,a,73,2008纽卡斯尔大学将从人类皮肤

19、细胞中提取的DNA注入来自母牛卵巢的卵子，卵子的所有遗传物质基本上都被去除。,3.3 Interspecies Embryos,2003上海第二医科大学盛慧珍教授研究组将人的体细胞核植入去核的兔卵细胞中。,a,74,3.4 Adult Stem Cells,do not raise the ethical questions that embryonic stem cells do because no embryos are needed exist in very small numbers often buried deep in the tissue mainly used for t

20、wo treatments: bone-marrow transplants to rebuild a patients immune system, and skin grafts to replace skin over a burn or other injury other applications for adult stem cells？use drugs to activate a patients own adult stem cells to perform the necessary repairs？,a,75,For a long time, scientists tho

21、ught that once a cell differentiated, it could never regain its pluripotency. They assumed that it must be set in its identity because it had so many genes turned on and off in ways particular to that cell type. In 2006, however, Kazutoshi Takahashi and Shinya Yamanaka of Kyoto University in Japan p

22、roved otherwise. They turned mouse skin cells specifically, fibroblasts into stem cells. These were the first induced pluripotent stem (iPS) cells.,3.5 Induced Pluripotent Stem Cells,a,76,The first direct reprogramming of adult human fibroblasts. Ian Wilmut Scottish Centre for Regenerative Medicine,

23、 University of Edinburgh In 2007 issues of Cell and Science, Yamanaka and colleagues (Takahashi et al., 2007) and Yu and colleagues (Yu et al., 2007) demonstrate that expression of four specific transcription factors gives adult human fibroblasts many of the characteristics of human embryonic stem c

24、ells. Refinements of this procedure will make it possible to produce pluripotent human cell lines without use of an embryo. There are profound scientific and social implications of this research.,Cell Stem Cell, 2007 Dec 13;1(6):593-4.,I decided a few weeks ago not to pursue nuclear transfer - the m

25、ethod used to create Dolly the sheep, he said, admitting the new method was easier to accept socially.,a,77,十年科学进展 1. The Dark Genome：基因组中的“暗物质” 3. Ancient DNA：古生物的DNA 5. Reprogramming Cells：细胞重编程 6. The Microbiome：人体内微生物组 8. Inflammation：炎症反应的阴暗面,Science, Dec. 2010,a,78,The Nobel Prize in Physiology or Medicine 2012. N. 21 Feb 2013 /nobel_prizes/medicine/laureates/2012/,The Nobel Prize recognizes two scientists who discovered that mature, specialised cells can be reprogrammed to become immature cells capable of developing into all t