STEM CELLS: The Upside and Downside of Stem Cell Science

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STEM CELLS The Upside and Downside of Stem Cell
Science
Human ES cell colony picture provided by Dr.
Toshihiko Ezashi
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Stem

• The main body or stalk of a plant
• The stock of a family lineage

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Specialized (differentiated) cells
Diploid, with 46 chromosomes
Haploid with 23 chromosomes
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The human body consists of more than 10 trillion
cells of more than 250 cell types
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What are stem cells?

• A stem cell has the ability to divide for
  indefinite number of divisions.
• Stem cells give rise to more specialized cells
  when they differentiate.
• There are three types of stem cell unipotent,
  lineage specific stem cells, adult stem cells
  (multipotent), embryonic stem cells
  (pluripotent).

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Real and Potential Applications of Stem Cells

• Bone marrow transplantation
• Transplantation medicine (diabetes, Parkinsons
  Disease stroke, arthritis, multiple sclerosis,
  heart failure spinal cord lesions)
• Drug testing
• Genetic change
• Other uses?

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UNIPOTENT STEM CELLS
P
M
N
H
Source NIH website Stem cells A Primer
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• ADULT STEM CELLS
• Undifferentiated, multipotent cells found in a
  differentiated tissue that can renew themselves
  and (with certain limitations) differentiate to
  yield all the specialized cell types of the
  tissue from which it originated, e.g stem cells
  from bone marrow that can give rise to all the
  blood cell types.

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Stem Cells versus Progenitor Cells
Niche Cells
Stem Cells
Progenitor cells
Precursor cells
Differentiated Cells
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PLURIPOTENT (Adult) STEM CELLS
Do such cells exist? Where? Are they an
alternative to pluripotent embryonic stem cells?
Source NIH website Stem cells A Primer
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ADULT STEM CELLS HAVE BROAD THERAPEUTIC
POTENTIAL (or do they?)
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ADULT STEM CELLS HAVE LIMITED THERAPEUTIC
POTENTIAL
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Embryonic stem cells

• Whats all the fuss about?

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• EMBRYONIC STEM CELLS
• Primitive (undifferentiated) cells, usually from
  the embryo, that have the potential to become a
  wide variety of specialized cell types.

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Establishment of Human Embryonic Stem Cells

• From spare IVF embryos
• Therapeutic cloning, i.e. by somatic cell nuclear
  transfer
• Induced pluripotent stem cells

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Dominic Doyle
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Bob Edwards and Patrick Steptoe
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Over Three Million IVF and Thousands of PGD
Babies have been Born!
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SEXUAL REPRODUCTION
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HUMAN ES CELLS
First isolated in 1998 from spare blastocysts
donated by an In Vitro Fertilization
(IVF) program
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Source NIH website Stem cells A Primer
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CONCERN

• Production of new human ES cells will involve the
  destruction of thousands of human embryos

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Facts

• Every year hundreds of thousands of human embryos
  are created by in vitro fertilization procedures
  designed to allow infertile couples to have
  children. To obtain eggs for IVF, eggs are
  produced by superovulation procedures
• Many more eggs are produced and fertilized than
  can possibly be used.
• Result embryos are discarded or stored
  indefinitely.

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ARE SUFFICIENT NUMBERS OF EMBRYONIC STEM CELL
LINES ADEQUATE FOR DEVELOPING THERAPIES?

• Different lines have different properties they
  dont all behave the same.
• Existing stem cells will never be useful for
  transplantation.
• Transplantation demands a close match between
  the donor and the recipient, e.g. kidney
  transplantation. Hence there is a requirement for
  large numbers of cell lines with different
  transplantation antigens on their surfaces.

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EMBRYONIC STEM CELLS FOR THERAPY

• How to direct their differentiation efficiently
  into specific cell types (e.g. pancreas, brain
  neurons).
• 2. How to deliver them efficiently for tissue
  repair.
• 3. How to prevent immune rejection.

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Establishment of Human Embryonic Stem Cells

• From spare IVF embryos
• Therapeutic cloning, i.e. by somatic cell nuclear
  transfer
• Induced pluripotent stem cells

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• NUCLEAR TRANSPLANTATION TO PRODUCE STEM CELLS

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February 1997 Cloning of Dolly reported
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Somatic Cell Nuclear Transfer Reproductive
Cloning
Sheep Cattle Goat Mule Pig Cat Mouse Rat Rabbit
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ABILITY TO PRODUCE STEM CELLS GENETICALLY
IDENTICAL TO PATIENT
Day 5
Therapeutic
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HOW DOES THIS RELATE TO HUMAN CLONING???
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CONCERN

• NUCLEAR TRANSPLANTATION WILL BE
• USED TO CLONE HUMAN BABIES.

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NUCLEAR TRANSPLANTATION TO PRODUCE STEM CELLS

• NO EMBRYONIC OR FETAL DEVELOPMENT BEYOND 200 CELL
  STAGE (SIZE OF TIP OF PIN)
• NO TRANSFER TO UTERUS
• BLASTOCYST OR STEM CELLS ALONE CANNOT PRODUCE A
  NEW INDIVIDUAL

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CONCERN

• Production of new human ES cells by somatic cell
  nuclear transfer will require an unlimited number
  of human oocytes from women donors

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CONCERN
HUMAN EGG DONORS WILL BE EXPLOITED
Day 5
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Establishment of Human Embryonic Stem Cells

• From spare IVF embryos
• Therapeutic cloning, i.e. by somatic cell nuclear
  transfer
• Induced pluripotent stem cells

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Pluripotent stem cells from adult fibroblasts
Lin28
Nanog
Takahashi (Yamanaka et al., Cell,2007 Yu
(Thomson) et al. Science 2007
Diagram from Zhares Scholer, Cell 2007)
Nanog Oct4 (POU domain transcription factor 5)
Sox2, sex determining region Y-box 2 (SRY) Klf4
(Kruppel-like factor 4) c-Myc viral oncogene
homolog Lin28 homolog
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Images of iPPC picked at day 30
GFP-PFF
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-1
0
2
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20 O2
4 O2
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Thank you
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Issues

• When does life begin? Missouri statutes indicate
  that human life begins at the moment of
  conception
• The new constitutional amendment and what it
  means
• But the sperm and the egg are alive
• The transition from an embryo to a baby is a
  gradual one
• Are embryos that cannot form a placenta or that
  are doomed to die before the differentiation of
  the main organ systems individuals?

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ARE SUFFICIENT NUMBERS OF EMBRYONIC STEM CELL
LINES ADEQUATE FOR DEVELOPING THERAPIES?
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Some Questions

• The status of hES cells. Are they the equivalent
  of embryos? Persons?
• What are the objections to using spare embryos?
• Are there alternatives to using hES cell lines
  for tissue replacement? Adult stem cells?
• Can hES cells be produced by developing cell
  lines from a biopsy of an embryo?
• Can embryos be created that lack any potential to
  develop into babies?