A Brief History of Neural Stem Cells

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INT 94JY Getting New Brain Cells Neurogenesis in
the Adult Brain Seminar 6 Adult Stem Cells.
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Embryonic Stem Cells Development
Proof of Principle Basis of all transgenic
Technology
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e.g. zygote
e.g. embryonic stem cell
Multipotent
e.g. adult stem cell
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Discovery of Adult Stem cells

• Till McColluch, 1961.
• Studying recovery from radiation poisoning via
  bone marrow transplants.
• Found colonies of transplanted cells formed in
  the spleen.

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Defining characteristics of Adult Stem Cells

• Proliferate
• Multipotential
• Last life-time
• (extensive self-renewal)

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Provide pool of cells for adult tissue
repair/turnover.
Can be maintained in vitro and transplanted for
repair.
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Adult vs Embryonic SCs

• Proliferate
• Multipotent
• Replace cells during turnover
• Repair damage to tissue.
• Last life time.

• Proliferate
• Pluripotent
• Important for development of tissue lineages
• Transient existence during early embryogenesis

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Hematopoietic/Blood Stem Cells (HSCs)

• HSC found in
• Bone marrow Umbilical cord Peripheral blood
  (need to mobilize via G-CSF)

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Fluorescent Activated Cell Sorting (FACS)
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Cell Sorting MACS vs FACS
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Enrichment/Purification of HSC by FACS
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HSC Repopulation Assay
Irradiate
Die in about 2 weeks
whole bone marrow
Live indefinitely
HSCs sorted from bone marrow
Live indefinitely
Single HSC
Live indefinitely
whole bone marrow without HSCs
Die in about 2 weeks
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HSC Serial Repopulation Assay
Irradiate
HSCs
Live indefinitely
HSCs
Irradiate
Live indefinitely
HSCs
Can go through 6 rounds of repopulation -extensive
self-renewal of HSCs -but limited! (not infinite)
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HSCs Leukemia Treatment
For more than 30 years, bone marrow (including
HSCs)s have been used to treat cancer patients
with conditions like leukemia and lymphoma.
Chemotherapy kills both leukemia cells and HSCs
without HSCs -gt die. If bone marrow HSCs are
removed before chemotherapy, then re-injected
after chemotherapy, HSC restore blood system -gt
live. (Can also get from donor but have problem
of tissue matching). -gtMore recently have used
purified HSC first stem cell therapy.
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What about HSCs and repair of other tissue?
Several studies have reported that
transplantation of an adult stem cell from one
tissue results in production of new cells in a
different tissue (even across lineages).
Plasticity of adult stem cells remain
controversial.
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Lineage Restriction, Plasticity,
Transdifferentiation
Transdifferentiation
De-differentiation
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Transdifferentiation versus Fusion
Transdifferentiation
Fusion
Mechanism(s) of SC plasticity remains unclear.
Further, may or may not be able to occur at level
sufficient for biological or clinical relevance.
Nuclear Separation
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Blood (hematopoietic) Stem Cells Summary
Individual cells in bone marrow can repopulate
blood system. -proliferate, -multipotential,
-last lifetime. -Unique gene expression
profile -gtthese are amazingly powerful SC as the
blood system containing trillions of cells turns
over every few days.
Proof of Principle Cancer (leukemia) treament
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