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Stem Cell
2. Capable of self-renewal(One daughter cell is like parent)
1. Capable of dividing and making new cells of many types
Differentiation: the process by which a cell undergoes a change to become a specialized cell type
Differentiation occurs step-by-step
Stem CellsPluripotent cell (Embryonic Stem Cell)
Multipotent cell (Adult Stem Cell)
Adult Mouse
Embryonic Stem Cells Bridge the Gap from theFertilized Egg to the Fully Formed Organism
Fertilized Egg
(“Totipotent”)
Embryo
(Cell Division and Differentiation)
(“Pluripotent” Cells)
Pancreas cell
Lens cell
Muscle cell
IMPORTANT!!!!!Each of these different
cell types has the same DNA
How do cells with the same DNA end up so different?
Gene A Gene B
MuscleCell
Gene A is on
Gene B is off
X
LensCell
Gene A is off
Gene B is on
PancreasCell
Gene A is on
Gene B is on
Protein A
DNA X
Embryonic Stem Cells1. Pluripotent2. Derived from the blastocyst 3-5 days after fertilization
ZygoteZygoteBlastocystBlastocyst
++
SpermSperm
EggEgg
FetusFetus
inner cell mass (embryo)
trophoblast (placenta)
Embryonic Stem Cells
A blastocyst contains 200-250 cells.The inner cell mass is only 30-34 cells
There are 10,000,000,000,000 cells in a human adult
And Where are the adult stem cells?
AdultstemcellsNeural Brain cell types
Skin Skin and hair
Gut Gut derivatives
eye Eye cell types
Blood & marrow Blood cell types
Each type of adult stem cell is found in the tissue it makes.
• mixed among the differentiated cells in that tissue
Different Types of Stem Cells: What and Where?
Embryonic Adult
• Isolate from inner cell mass of embryo (blastocyst stage)
• Found in from adult tissue (but for most types we don’t know how to find them)
• Can make all cell types (TOTIPOTENT)
• Only make certain cell types (MULTIPOTENT)
Potential:
How they are obtained:
Replacement is permanent! (stem cells are self-maintaining)
Stem cells could replace dead or damaged cells
Stem cells could be transplanted directly into diseased tissue where they would become the desired cell type
or
Stem cells could be coaxed into specializing in the lab and then transplanted as differentiated tissue
A bone marrow transplant isan adult stem cell transplant
1. Stem cells contribute to all blood cell types
2. After several months, the new cells still populate blood
Leukemia(remove bone marrow)
Blood Cells Regenerated
Implant with Blood Stem Cells
Challenge 2: Not easily accessible in all tissues
Brain
Muscles
How are we going to get stem cells from the brain of the patient??
Challenge 3. Rare & Difficult to isolate
Need “markers” to differentiate stem cells from other types of cells
Embryonic vs. Adult Stem Embryonic vs. Adult Stem CellsCells
Embryonic Stem Cells
• Technical difficulties: How to direct specific differentiation
• Controversy: Ethical considerations
Adult Stem Cells
• Technical difficulties: Need to improve isolation techniques and optimize culturing conditions
Embryonic stem (ES) cells may be used to treat deteriorating brain cells
Parkinson’s Disease: Selective death of subset of neurons
Mouse model of Parkinson’s disease
Inject mouse ES cellsInto diseased brain
2. Still in experimental infancy, but shows much promise for many diseases.
1. Could be used to treat Alzheimer’s, Huntington’s,spinal cord injury, etc…
Partial replacement of lost neurons
Where do the blastocysts come from?
In vitro fertilization
• Aim to help infertile couples conceive children
• Egg is fertilized with sperm in the lab
Zygote Blastocyst
Sperm
Egg
Fertilization
LAB
Problem of immune rejection• Each person has own unique set of DNA
• Body’s immune system rejects cells that do not belong to the individual
• Need to match donor cells/tissues/organs to recipient
• Stem cells used must be genetically compatible with patient
• Embryonic stem cell lines derived from IVF will not be compatible Somatic Cell Nuclear Transfer (SCNT) = THERAPEUTIC CLONING
Somatic cell nuclear transfer (SCNT)
• Somatic Cell = Any cell of the body, except sperm and egg
• Nuclear Transfer = Moving the genetic material (DNA) of one cell to another
• Nucleus of an egg is removed and replaced with the DNA of an adult cell
• Creates patient-specific ES cell line
What is cloning?
• Clones = INDIVIDUALS that are genetically identical to another
Identical twins are clones
• Clones = CELLS that are genetically identical to another
=
Need to be implanted into a surrogate mother
“Personalized”Stem cells for tissue
therapy
REPRODUCTIVE CLONING
THERAPEUTIC CLONING