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Stem Cells What They Are and What They Do February 22, 2008. UNDIFFERENTIATED AND ABLE TO DIVIDE INDEFINITELY. STEM CELLS HAVE 3 BASIC PROPERTIES. 2. CAPABLE OF SELF-RENEWAL. 1. 3. D n. D 1. D 2. CAPABLE OF DIFFERENTIATION INTO - PowerPoint PPT Presentation
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Stem CellsStem Cells What They Are and What What They Are and What
They DoThey DoFebruary 22, 2008February 22, 2008
STEM CELLS HAVE 3 STEM CELLS HAVE 3 BASIC PROPERTIESBASIC PROPERTIES
11 22
33
D1 D2........ Dn
CAPABLE OF CAPABLE OF SELF-RENEWALSELF-RENEWAL
UNDIFFERENTIATED UNDIFFERENTIATED AND ABLE TO DIVIDE AND ABLE TO DIVIDE INDEFINITELY INDEFINITELY
CAPABLE OF DIFFERENTIATION INTOCAPABLE OF DIFFERENTIATION INTO DIFFERENT CELL TYPESDIFFERENT CELL TYPES
Adapted from Caltech 2000Adapted from Caltech 2000
Types of Stem CellsTypes of Stem Cells
Adapted from www.nih.govAdapted from www.nih.gov
Formation of BlastocystFormation of Blastocyst
Creation of Embryonic Stem Creation of Embryonic Stem (ES) Cells(ES) Cells
Derivation of Human ES Derivation of Human ES CellsCells
From Geron Inc.From Geron Inc.
Embryonic Stem (ES) Embryonic Stem (ES) CellsCells
ES cell colonyES cell colony
FeederFeedercellscells
Heart Cells Derived from Heart Cells Derived from ES CellsES Cells
Examples of Potential Examples of Potential Clinical Uses of Stem CellsClinical Uses of Stem Cells
Regenerate the heart after myocardial Regenerate the heart after myocardial infarction.infarction.
Cure diabetes by transplanting cells that Cure diabetes by transplanting cells that produce insulin into the pancreasproduce insulin into the pancreas
Regenerate kidneys obviating the need for Regenerate kidneys obviating the need for dialysisdialysis
Regenerate hair follicles in aging Regenerate hair follicles in aging scientistsscientists
Regenerate the nervous system in many Regenerate the nervous system in many disorders ( Parkinson’s Disease, stroke, disorders ( Parkinson’s Disease, stroke, spinal cord injury etc.)spinal cord injury etc.)
Problem: Like all transplanted tissues, Problem: Like all transplanted tissues, transplanted stem cells may potentially transplanted stem cells may potentially be rejected by the host immune system.be rejected by the host immune system.
Problem: Genetic mismatches between Problem: Genetic mismatches between donor and host tissues may lead to donor and host tissues may lead to abnormal cell-cell signalingabnormal cell-cell signaling
and/or dysregulation of organ function.and/or dysregulation of organ function.
Creation of ES Cells by Creation of ES Cells by Nuclear TransferNuclear Transfer
www.nih.govwww.nih.gov
Somatic Cell Nuclear Somatic Cell Nuclear TransferTransfer
(“therapeutic cloning”)(“therapeutic cloning”)
OocyteOocyte
blastocystblastocyst
somatic cellsomatic cell
Create an ES cell line withthe patient’s own genes (DNA)
Deriving Pluripotent Deriving Pluripotent Stem CellsStem Cells
from Skin Cellsfrom Skin Cells
Types of Stem CellsTypes of Stem Cells
MULTIPOTENT STEM CELLS EXIST IN MULTIPOTENT STEM CELLS EXIST IN BOTH EMBRYOS AND ADULTSBOTH EMBRYOS AND ADULTS
STEM CELLS IN EMBRYOSTEM CELLS IN EMBRYO
STEM CELLS IN ADULTSTEM CELLS IN ADULT
NEWLY-NEWLY-FORMEDFORMED
TISSUES ANDTISSUES ANDORGANSORGANS
Adapted from Caltech 2000Adapted from Caltech 2000
NATURALNATURALTURNOVERTURNOVER
REGENER-REGENER-ATIONATION
Multipotent Stem CellsMultipotent Stem Cells In each organ of the body, most cells In each organ of the body, most cells
types arise during development from an types arise during development from an organ-specific stem cell.organ-specific stem cell.
Most organs seem to have some stem Most organs seem to have some stem cells remaining even in the adult. The cells remaining even in the adult. The existence of specific islet cell and existence of specific islet cell and cardiomyocyte precursors is cardiomyocyte precursors is controversial.controversial.
There is some “plasticity” i.e. fat stem There is some “plasticity” i.e. fat stem cells or bone marrow stem cells can cells or bone marrow stem cells can generate brain cells. However most generate brain cells. However most apparent transdifferentiation apparent transdifferentiation in vivoin vivo actually reflects cell fusion.actually reflects cell fusion.
Neural Stem CellsNeural Stem Cells
NeuronsNeurons
Oligodendrocytes Oligodendrocytes (myelin)(myelin)
AstrocytesAstrocytes
The same stem cell can generate all of The same stem cell can generate all of
the major cell types in the brainthe major cell types in the brain
Clinical applications:Clinical applications:
•Generation of neurons to repair Generation of neurons to repair areas of brain irrespective of the areas of brain irrespective of the cause of the damage.cause of the damage.
•Generation of oligodendroglia to Generation of oligodendroglia to facilitate remyelination (e.g. in facilitate remyelination (e.g. in multiple sclerosis or spinal cord multiple sclerosis or spinal cord injury).injury).
•Generation of astrocytes as a vehicle Generation of astrocytes as a vehicle for gene therapy or drug therapy.for gene therapy or drug therapy.
Question:Question: How will a cellular How will a cellular microenvironment be created microenvironment be created in vivo in vivo that that fosters organ regeneration?fosters organ regeneration?
11nm
Collagen Fibril Architecture in Nanostructures is Useful to
Regenerate Body Parts
A nanoscale cylinder with highlyordered surface to deliver biologicalinformation--peptides
S.I. StuppNorthwestern University
Mineral Nucleation Region
Bioactive Region
Crosslinkable Region
Bioactive Peptide-Amphiphiles
Hydrophobic Tail
Science, 294, 1684 (2001)C10CCCCGGGS(P)RGD (-3)
Self-Assembly into Cylindrical Nanostructures
Scanning EM of GelScanning EM of Gel
ConclusionsConclusions Stem cell biology promises to Stem cell biology promises to
revolutionize the practice of medicine. revolutionize the practice of medicine. Therapies will be come available for many Therapies will be come available for many previously untreatable diseases.previously untreatable diseases.
There are several types of stem cells that There are several types of stem cells that may potentially be used for such may potentially be used for such therapies.therapies.
The embryonic stem cell has the most The embryonic stem cell has the most potential, but significant ethical/political potential, but significant ethical/political issues remain to be resolved.issues remain to be resolved.
Neurology – a visionNeurology – a vision
Regenerative strategies will Regenerative strategies will revolutionize the field of neurology. revolutionize the field of neurology. Disorders such as stroke, Parkinsons Disorders such as stroke, Parkinsons disease, spinal cord injury, traumatic disease, spinal cord injury, traumatic brain injury, multiple sclerosis, and brain injury, multiple sclerosis, and others will be treatable.others will be treatable.