dasar stem cell dan pengembangan terapi organ prof. dr. marlina, ms, apt seminar nasional farmasi...
DESCRIPTION
What are stem cells? Stem cells are undifferentiated cells that have many potential scientific uses: Stem cells are undifferentiated cells that have many potential scientific uses: Cell based therapies Cell based therapies Often referred to as regenerative or reparative medicine Often referred to as regenerative or reparative medicine Therapeutic cloning Therapeutic cloning Gene therapy Gene therapy Cancer research Cancer research Basic research Basic researchTRANSCRIPT
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DASAR STEM CELL DAN PENGEMBANGAN
TERAPI ORGAN
Prof. Dr. Marlina, MS, Apt
Seminar Nasional FarmasiRocky Hotel, Padang, 23 Juni 2012
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STEM CELL RESEARCH - WHAT IS IT ALL ABOUT?
http://stemcells.nih.gov/info/basics/ "Image courtesy of NIH resource for stem cell research"
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What are stem cells? Stem cells are undifferentiated cells that
have many potential scientific uses: Cell based therapies
Often referred to as regenerative or reparative medicine
Therapeutic cloning Gene therapy Cancer research Basic research
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Two types of stem cells
Embryonic Stem Cells (ESC): received from: Embryos created in vitro fertilization Aborted embryos
Adult Stem Cells (ASC): can be received from: Limited tissues (bone marrow, muscle,
brain)Discrete populations of adult stem cells
generate replacements for cells that are lost through normal wear and tear, injury or disease
Placental cord
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“ADULT” STEM CELLS ARE OBTAINED IN A VARIETY OF WAYS
Illustration by Matt Bohan, 2007
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STEM CELLS HAVE ALSO BEEN FOUND IN “MATURE”
ORGANS
Illustration by Matt Bohan, 2007
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Source of ESC Blastocyst
3-5 day old embryo Stem cells give rise to multiple
specialized cell types that make up the heart, lung, skin, and other tissues
Human ESC were only studied since 1998 It took scientists 20 years to learn how
to grow human ESC following studies with mouse ESC
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How are embryonic stem cells harvested?
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)
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Blastocyst
http://www.ivf-infertility.com/infertility/infertility5.php
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Unique characteristics of Stem Cells
Stem cells can regenerate Unlimited self renewal through cell
division Stem cells can specialize
Under certain physiologic or experimental conditions
Stem cells then become cells with special functions such as:Beating cells of the heart muscleInsulin-producing cells of the pancreas
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Self - Renewal (Regeneration)
Stem cells are capable of dividing & renewing themselves for long periods This 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 unspecializedThese cells are capable of long-term self-renewal
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Specialization of Stem Cells: Differentiation
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
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Potential of Stem Cells
Totipotent (total): Total potential to differentiate into
any adult cell type Total potential to form specialized
tissue needed for embryonic development
Pluripotent (plural): Potential to form most or all 210
differentiated adult cell types
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Multipotent (multiple): Limited potential Forms only multiple adult cell
typesChondrocyteNeurons
Unipotent – these cells only produce one cell type., but have the property of self renewal which distinguishes them from the non stem cells.
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http://www.stemcellresearch.org/testimony/20040929prentice.htm Reprinted with permission of Do No Harm.
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Adult Stem CellsAdult or somatic stem cells
have unknown origin in mature tissuesUnlike embryonic stem cells, which are defined by their origin (inner cell mass of the blastocyst)
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Potential of Adult Stem Cells
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Adult stem cells continued
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 typesThis is known as PLASTICITY
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Adult Stem Cell Plasticity Examples
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!
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Adult stem cells: A brief history
Adult stem cell research began about 40 years ago
Stem cell discoveries in 1960s: Bone marrow contains 2 populations of
stem cellsHematopoietic stem cells – forms all
blood cell typesBone 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
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History Cont. Stem Cell
Discoveries in the 1990s Neural stem cells in
brain are able to generate the brain’s three major cell types
Astrocytes Oligodendroglial
cells Neurons
http://www.alsa.org/images/cms/Research/Topics/cell_targets.jpg
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Potential Uses of Stem Cells
Basic research – clarification of complex events that occur during human development & understanding molecular basis of cancerMolecular mechanisms for gene control
Role of signals in gene expression & differentiation of the stem cell
Stem cell theory of cancer
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Potential uses cont. Biotechnology(drug discovery &
development) – stem cells can provide specific cell types to test new drugs Safety testing of new drugs on
differentiated cell lines Screening of potential drugs
Cancer cell lines are already being used to screen potential anti-tumor drugs
Availability of pluripotent stem cells would allow drug testing in a wider range of cell types & to reduce animal testing
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Potential uses cont. Cell based therapies:
Regenerative therapy to treat Parkinson’s, Alzheimer’s, ALS, spinal cord injury, stroke, severe burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis
Stem cells in gene therapyStem cells as vehicles after they have
been genetically manipulated Stem cells in therapeutic cloning Stem cells in cancer
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Embryonic vs Adult Stem Cells
Totipotent Differentiation
into ANY cell type Known Source Large numbers can
be harvested from embryos
May cause immune rejection Rejection of ES
cells by recipient has not been shown yet
Multi or pluripotent Differentiation into
some cell types, limited outcomes
Unknown source Limited numbers,
more difficult to isolate
Less likely to cause immune rejection, since the patient’s own cells can be used
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Application of stem cells
Stem cell research:1. It provides an ideal model
for the study of development of organisms
2. It replaces damaged cells of the body
3. It also aids in drug discovery
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Regenerative medicine andTherapeutic issues
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Bone marrow transplant:Example of adult stem cell-based
therapy
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Haematopoeitic stem cells
Derived from bone marrow in adults and umbilical cord blood
Option given to the parents regarding stem cell banking during antenatal visits
25% chance that sibling also can have a perfect match
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The Nobel Prize, 1990
E. Donnall Thomas
first succsessful HSCT in treatment of acute leukemias
Thomas ED, Lochte HL, Lu WC, Ferrebee JW. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N. Engl. J. Med.
1957; 257: 491.
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Blood is collected from umb cord immediately after delivery about 100-150cc
The number of cells in 1 ml is 40,000
They are stored in blood banks at -196deg celsius in a state of suspended animation and restart their activity on thawing
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Hematopoietic and Stromal Adult Stem Cell Differentiation
stemcells.nih.gov/.../images/figure2_lg.jpg
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Ailments for which stem cells are being
used now Acute leukemias
Chronic leukemias
Myelodysplastic syndromes
Marrow failure Myeloprolifera
tive disorders Lymphoprolife
rative disorders
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Trials underway Cardiac disease Diabetes Multiple Sclerosis Muscular Dystrophy Parkinson’s disease Spinal cord injury Stroke
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Cell Therapy in Failing Heart GOAL
Transfer of functional myocytes to heart – Improve its function
The DEALS “ Homing of grafted cells” Engraft into non functional scar Electromechanical coupling and synchronisation Neo angiogenesis and myogenesis Good craft survival Low immunogenecity Ethical acceptance Low oncogenicity Case of application
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Stem cells for myocardial regeneration
HETEROLOGOUS• Fetal
cardiomyocytes• Embryonal stem
cells
AUTOLOGOUS•Skeletal myoblast•Endothelial progenitors•Bone marrow stem cells
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Stem cells therapy
Cardiovascular note Infarct repair Cardiomyopathy treatment End stage coronary artery disease
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Bone marrow stem cells
Hemapoeitic Stem cells T-2%
Endothelial Progenitor cells <0.05% (Stromal stem cells)
(Lin – c Kit (+ve) ; AC 133+)
Transplantation HEART Translocation(Endogenous stem cell mobilization)
CARDIOMYOCYTESEndothelium sm cells
G – CSFGM - CSF
CD 34+
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Diabetes ResearchWhat is known cells are not generated from
adult stem cells in the pancreas. It is unlikely that a cure for
diabetes will come from adult stem cells.
Embryonic stem cells have been shown to generate insulin-producing cells.
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What Has Been Tried:Whole organ pancreas transplants
Problem: not enough organs to meet the demand
Problem: must take powerful immunosuppressants
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What Has Been Tried:
Injections of pancreatic islet cellsProblem: less than 8% of
these transplants have been successful
Problem: immunosuppressants are required
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Problem: There is much work to be done before this technique will be ready—if it is ever ready.
Possible Next Step:Inject cells into the patient’s pancreas
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Possible Next Step:Activate cells in the patient’s own pancreas Problem: There may be no
cells left in the pancreas of a patient to activate.
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Possible Next Step
Provide type l diabetics with transplants of cells derived from embryonic stem cells.
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What We Need to Know What properties make
embryonic stem cells unique? Where do these cells come
from? How are they involved in the
formation of the pancreas, cells, and other tissues?
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What makes them unique?
can regenerate an infinite number of times
can be grown in culture indefinitely
are classified as pluripotent
are able to differentiate into specialized cells as needed
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Germ Layer Differentiation
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Forming Specialized Cells
Growth factors and other signals tell a stem cell when to differentiate and what type of cell to become.
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Forming Specialized Cells
The same growth factors and signals could be used to direct the differentiation of human embryonic stem cells grown in culture.
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What is Known
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