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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
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UNDIFFERENTIATED AND ABLE TO DIVIDE INDEFINITELY STEM CELLS HAVE 3 BASIC PROPERTIES 2 CAPABLE OF SELF-RENEWAL 1 3 ........ Dn D1 D2 CAPABLE OF DIFFERENTIATION INTO DIFFERENT CELL TYPES Adapted from Caltech 2000
Types of Stem Cells • Adapted from www.nih.gov
Derivation of Human ES Cells From Geron Inc.
Feeder cells ES cell colony Embryonic Stem (ES) Cells
Examples of Potential Clinical Uses of Stem Cells • Regenerate the heart after myocardial infarction. • Cure diabetes by transplanting cells that produce insulin into the pancreas • Regenerate kidneys obviating the need for dialysis • Regenerate hair follicles in aging scientists • Regenerate the nervous system in many disorders ( Parkinson’s Disease, stroke, spinal cord injury etc.)
Problem: Like all transplanted tissues, transplanted stem cells may potentially be rejected by the host immune system. • Problem: Genetic mismatches between donor and host tissues may lead to abnormal cell-cell signaling and/or dysregulation of organ function.
Creation of ES Cells by Nuclear Transfer www.nih.gov
blastocyst Create an ES cell line with the patient’s own genes (DNA) Oocyte somatic cell
MULTIPOTENT STEM CELLS EXIST IN BOTH EMBRYOS AND ADULTS STEM CELLS IN EMBRYO STEM CELLS IN ADULT NEWLY- FORMED TISSUES AND ORGANS Adapted from Caltech 2000 NATURAL TURNOVER REGENER- ATION
Multipotent Stem Cells • In each organ of the body, most cells types arise during development from an organ-specific stem cell. • Most organs seem to have some stem cells remaining even in the adult. The existence of specific islet cell and cardiomyocyte precursors is controversial. • There is some “plasticity” i.e. fat stem cells or bone marrow stem cells can generate brain cells. However most apparent transdifferentiation in vivo actually reflects cell fusion.
The same stem cell can generate all of the major cell types in the brain Clinical applications: • Generation of neurons to repair areas of brain irrespective of the cause of the damage. • Generation of oligodendroglia to facilitate remyelination (e.g. in multiple sclerosis or spinal cord injury). • Generation of astrocytes as a vehicle for gene therapy or drug therapy.
Question: How will a cellular microenvironment be created in vivo that fosters organ regeneration?
Collagen Fibril Architecture in Nanostructures is Useful to Regenerate Body Parts A nanoscale cylinder with highly ordered surface to deliver biological information--peptides 11nm S.I. Stupp Northwestern University
Bioactive Peptide-Amphiphiles Mineral Nucleation Region Hydrophobic Tail Crosslinkable Region Bioactive Region Science, 294, 1684 (2001) C10CCCCGGGS(P)RGD (-3)
Conclusions • Stem cell biology promises to revolutionize the practice of medicine. Therapies will be come available for many previously untreatable diseases. • There are several types of stem cells that may potentially be used for such therapies. • The embryonic stem cell has the most potential, but significant ethical/political issues remain to be resolved.
Neurology – a vision Regenerative strategies will revolutionize the field of neurology. Disorders such as stroke, Parkinsons disease, spinal cord injury, traumatic brain injury, multiple sclerosis, and others will be treatable.