Stem Cells Flashcards
Stem Cell
• A primitive cell; can either self-renew or give rise to more specialized cell types
• Single stem cells differentiate into multiple, functional cell types
– Progenitors are more differentiated
• Stem cells functionally reconstitute a given tissue in vivo
– For example, one blood stem cell gives rise to red cells, white cells and platelets
Characteristics of Stem Cells
– Notterminallydifferentiated
– Candividewithoutlimit
– Undergo slow division
–When divide gives rise to 1 cell with stem cell characteristics and the other with the ability to be differentiated
Adult stem cells are…
tissue specific
Totipotency
Ability to give rise to all cells of an organism, including embryonic and extraembryonic tissues (cells which support embryonic development). A zygote is totipotent.
Pluripotency
Ability to give rise to all cells of the embryo and subsequently adult tissues. (embryonic stem cells)
Multipotency
Ability to give rise to different cell types of a given lineage. (adult stem cells)
Founder stem cells
-Programmed to have fixed number of divisions
• Controlled by short range signals that operate for a few hundred cell diameters
• Define the size of large final structures
Transit Amplifying Cells
- cells that divide frequently
- transit from a cell with stem cell characteristics to a differentiated cell
- leave the basal layer and incorporate into the layers above
Maintenance of stem cells
For a steady pool of stem cells, 50% of daughter cells must remain as stem cellsretain original DNA
Divisional vs. Environmental Asymmetry
- how maintenance of stem cells is accomplished
a. asymmetric division may create 2 cells, one with stem cell characteristics and another with factors that give it the ability to differentiate
b. Division makes 2 identical cells but environment may influence/alter 1 cell
Immortal Strand Hypothesis
• Some tissues’ stem cells selectively retain original DNA
– A way to prevent genetic errors in stem cells
• This daughter cell will retain stem cell
characteristics
• Original strand of DNA preserved in stem cells from generation to generation
• Second cell gets the newly synthesized strand
Embryonic Stem Cells
- Derived from the blastocyst stage of embryo
- Capable of proliferating indefinitely in culture
- Unrestricted developmental potential
- When put back in blastocyst they can integrate well with the embryo
- Develop into different cell types
- If injected into an embryo at a later stage or into an adult they fail to receive appropriate sequence of cues for proper differentiation
- Can become a tumor
ES Cell Therapies
• Reliable, highly reproducible results; establishes pluripotency
• They provide a solid theoretical and experimental foundation to:
– Induce development of specialized cell types
– Solve rejection problems
• Have good growth properties
• Promising “proof-of-principle” research
• Successful treatment of animal models of disease with mouse ES cells
– Severe immune deficiency
– Diabetes
– Parkinson’s disease
– Spinal injury
– Demyelination
– Myocardial infarction
Genes in Pluripotent cells
• Human ES cells express genes found in pluripotent cell populations – Many of these code for proteins with important roles in early embryonic
development
• Transcription factors (Nanog, Oct4, Sox2 and FoxD3) essential for establishment and maintenance of pluripotent stem cells in the embryo
– GCNF is required for early stages of pluripotent cell differentiation
– Cripto and GDF-3 are growth factors found in pluripotent cells
• There may be a common molecular blueprint of gene expression in pluripotent stem cells
Adult Stem Cells
• Found in tissues; responds to demands of growth/repair
• Tissue organization, growth, repair require restrictions on developmental potential of adult stem cells
• Strictly imposed by molecular restraints on gene expression
– Heritable during many rounds of cell division
• Adult stem cell may show relaxation of these restrictions in an altered environment, possibly accounting for plasticity
– Observed usually at low frequency
Applications in Adult Stem Cells
• Restricted capacity and growth potential
• Harvested cells retain properties of the original tissue type; have memory of its developmental history
– Cannot coerce to express the characteristics of a radically different tissue type
– Limits clinical use
• Few, recent experiments suggest more potential than originally thought.
– Not yet reproducible
– Characterized by flawed design, flawed assays, or poor quality data
Hematopoietic and Stromal Stem Cell
- Both come from bone marrow
- Differ in what they can be differentiated as
- HSCs: blood components
- MSCs: connective tissues, tissues
Cord Blood
-Undifferentiated
• No gene manipulation
Transcription factors essential for pluripotent cells
Mango, oct4, sox2, and foxD3
GCNF
Required for early stages of pluripotent cell differentiation
Cripto and GDf-3
Growth factors found in pluripotent cells
Hematopoietic stem cells
- blood components
- found in cord blood, bone marrow, and peripheral blood
Stromal stem cells
- connective tissues, tissues
- found in bone marrow, Wharton’s jelly, adipose tissue, and tooth pulp
Immune Rejection
Genetically different, grafted cells can be rejected by host (requires identical genome)
-somatic cell nuclear transfer can limit rejection
Induced Pluripotent stem cells
Take adult fibroblast and inject it with Oct3/4, Sox2, Nanog, LIN-28, KFL4, c-Myc which then forms iPs cells and they can be divided into many different types
Done by viruses
High potential of teratoma
SCNT
Prohibiting cloning at this step restricts any therapeutic application
Blastocyst step in SCNT
Prohibiting implantation restricts reproduction but allows therapeutic research to continue
Bands
Immature neutrophils with banded nucleus
-only seen with really bad infections
