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What are Stem Cells? Potential Uses Claims Against Using Stem Cells Cultivation Process Stem Cells and Cloning Stem Cell Theory of Cancer Worldwide Status
Stem cells are undifferentiated cells that have many potential scientific uses:
Cell
based therapies
Therapeutic
Discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury or disease
Placental
Source of ESC
Blastocyst
ball
of cells 3-5 day old embryo Stem cells give rise to multiple specialized cell types that make up the heart, lung, skin, and other tissues
took scientists 20 years to learn how to grow human ESC following studies with mouse ESC
Human ES cells are derived from 4-5 day old blastocyst Blastocyst structures include:
Trophoblast:
outer layer of cells that surrounds the blastocyst & forms the placenta Blastocoel: (blastoseel) the hollow cavity inside the blastocyst that will form body cavity Inner cell mass: a group of approx. 30 cells at one end of the blastocoel:
Forms 3 germ layers that form all embryonic tissues (endoderm, mesoderm, ectoderm)
Blastocyst
http://www.ivf-infertility.com/infertility/infertility5.php
certain physiologic or experimental conditions Stem cells then become cells with special functions such as:
Beating cells of the heart muscle Insulin-producing cells of the pancreas
Unspecialization
do not have any tissue-specific structures that allow for specialized function Stem cells cannot work with its neighbors to pump blood through the body (like heart muscle cells) They cannot carry molecules of oxygen through the bloodstream (like RBCs) They cannot fire electrochemical signals to other cells that allow the body to move or speak (like nerve cells)
Stem cells are capable of dividing & renewing themselves for long periods
is unlike muscle, blood or nerve cells which do not normally replicate themselves In the lab, a starting population of SCs that proliferate for many months yields millions of cells that continue to be unspecialized
This
Differentiation: unspecialized stem cells give rise to specialized (differentiated) cells in response to external and internal chemical signals
Internal
signals: turn on specific genes causing differential gene expression External signals include:
Chemicals secreted by other cells such as growth factors, cytokines, etc. Physical contact with neighboring cells
Differentiation
Why do your body cells look different although they all carry the same DNA, which was derived from one fertilized egg? Differentiation example
(http://learn.genetics.utah.edu/units/biotech/microarray/)
Totipotent (total):
Total
potential to differentiate into any adult cell type Total potential to form specialized tissue needed for embryonic development
Pluripotent (plural):
Potential
cell types
Multipotent (multiple):
Limited
embryonic stem cells, which are defined by their origin (inner cell mass of the blastocyst)
Adult stem cells typically generate the cell types of the tissue in which they reside
Stem
cells that reside in bone marrow give rise to RBC, WBC and platelets Recent experiments have raised the possibility that stem cells from one tissue can give rise to other cell types
Blood cells becoming neurons Liver cells stimulated to produce insulin Hematopoietic (blood cell producing) stem cells that become heart cells
CONCLUSION: Exploring the use of adult stem cells for cell-based therapies has become a very important (and rapidly increasing) area of investigation by research scientists!
Bone
cells
Hematopoietic stem cells forms all blood cell types Bone marrow stromal cells mixed cell population that generates bone, cartilage, fat and fibrous connective tissue
Rat
brain contains two regions of dividing cells, which become nerve cells
History Cont.
stem cells in brain are able to generate the brains three major cell types
http://www.alsa.org/images/cms/Research/Topics/cell_targets.jpg
Adult stem cells were found in many more tissues than expected Some may be able to differentiate into a number of different cell types, given the right conditions General consensus among scientist:
Adult
CLARIFICATION: not all new adult cells arise from stem cells
Most
Basic research clarification of complex events that occur during human development & understanding molecular basis of cancer
Molecular
mechanisms for gene control Role of signals in gene expression & differentiation of the stem cell Stem cell theory of cancer
Biotechnology(drug discovery & development) stem cells can provide specific cell types to test new drugs
Safety
therapy to treat Parkinsons, Alzheimers, ALS, spinal cord injury, stroke, severe burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis Stem cells in gene therapy
Stem
Totipotent
Differentiation
Multi or pluripotent
Differentiation
into ANY
cell type
Known Source Large numbers can be harvested from embryos May cause immune rejection
Rejection
Unknown source Limited numbers, more difficult to isolate Less likely to cause immune rejection, since the patients own cells can be used
Difficult to establish and maintain * Difficulty in obtaining pure cultures from dish* Potential for tumor formation and tissue* destruction Questions regarding functional differentiation Immune rejection Genome instability Few & modest results in animals, no clinical treatments * = same problem Ethically contentious
with ASC
cells provide ES cells with a sticky surface for attachment Feeder cells release nutrients
Recent discovery: methods for growing embryonic stem cells without mouse feeder cells
Significance
ES cells are removed gently and plated into several different culture plates before crowding occurs
http://www.news.wisc.edu/packages/stemcells/illustration.html Images depict stem cell research at the University of Wisconsin Madison.
Purpose:
Reproductive
cloning in animals Therapeutic cloning in animals Breeding animals or plants with favorable traits Producing TRANSGENIC animals that:
Make a therapeutic product (vaccine, human protein etc) Act as animal models for human disease Deliver organs that will not be rejected (cells lacking cell surface markers that cause immune rejection)
Vaccines
gene
cloning such as cloning an embryo Regenerative cloning to produce customized stem cells & overcome immune rejection
must be implanted into surrogate mom Surrogate mom is just a container that provides protection & chemical signals necessary for development
http://www.kumc.edu/stemcell/early.html Reprinted with permission from the University of Kansas Medical Center.
Obstacles:
Very
inefficient process Most clones have deleterious effects & die early Surviving clones show premature aging signs Signs of abnormal embryonic development:
Clones & their placentas grow much faster than expected in surrogate mom
Therapeutic Cloning
Correct
1% of the DNA in the clone will NOT be identical to donor cell (patient) It will be identical to egg cell used in SCNT REASON: mitochonrial DNA in eggs
Human mitochondria carry about 13 genes, some of which code for surface proteins
Excessive
hormone treatment of females to induce high rate of ovulation Surgery to retrieve eggs
Both can be harmful to female human Cow/pig females may be used
Cow/pig
Common Opinions
Reproductive cloning is a criminal offense (it is ILLEGAL worldwide!) Therapeutic cloning is acceptable, however there is still significant controversy over whether:
the clone is implanted into the uterus of surrogate mom? OR the clone is explanted into culture dish to generate ES cells
examination of tumor samples revealed many morphological (structural & functional) resemblances to ESC in a developing fetus
represents a ball of almost all cell types This indicates that teratoma may originate from unregulated stem cells that can give rise to almost all tissues
Teratoma
Ovarian Teratoma
You
Tumor cell
Determine difference between cancer & normal stem cells Identify potential points in pathways critical for the survival of cancer SCs Develop therapies that specifically target cancer SC Duke University Explanation
Great Britain
Very liberal policies on research Therapeutic cloning allowed, use of excess embryos & creation of embryos allowed Stem cell research allowed Less liberal politics Use of excess embryos from IVF allowed Reproductive AND therapeutic cloning banned Very strict policies Use of excess embryos and creation of embryos banned Scientists can IMPORT embryos
France
Germany
Debate in US
Federal funding available for research using the Bush lines only:
ES
of human embryos for IVF & therapeutic cloning is legal in most states
No federal funding
Some
Global Status
References
Stem cells & Cloning Stem cells & Cloning; David A. Prentice, Benjamin Cummings, 2003 http://www.pbs.org/wgbh/nova/sciencenow/3302/06.html http://www.stemcellresearch.org http://www.stemcells.nig.gov/info/nasics/nasics7.asp http://www.stemcells.nig.gov/info/scireport/2006report.ht m http://www.whitehouse.gov/news/re;eases/2001/08/2001 0809-2.html Stem cells in class; Badran, Shahira; Bunker Hill Community College, 2007, Boston Museum of Science Biotechnology Symposium Harvard Stem Cell Institute