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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 * * * * * * * * * * * * 1997 Ian Wilmut ... – PowerPoint PPT presentation

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Title: STEM CELLS: The Upside and Downside of Stem Cell Science


1
STEM CELLS The Upside and Downside of Stem Cell
Science
Human ES cell colony picture provided by Dr.
Toshihiko Ezashi
2
Stem
  • The main body or stalk of a plant
  • The stock of a family lineage

3
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4
Specialized (differentiated) cells
Diploid, with 46 chromosomes
Haploid with 23 chromosomes
5
The human body consists of more than 10 trillion
cells of more than 250 cell types
6
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).

7
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?

8
UNIPOTENT STEM CELLS
P
M
N
H
Source NIH website Stem cells A Primer
9
  • 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.

10
Stem Cells versus Progenitor Cells
Niche Cells
Stem Cells
Progenitor cells
Precursor cells
Differentiated Cells
11
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
12
ADULT STEM CELLS HAVE BROAD THERAPEUTIC
POTENTIAL (or do they?)
13
ADULT STEM CELLS HAVE LIMITED THERAPEUTIC
POTENTIAL
14
Embryonic stem cells
  • Whats all the fuss about?

15
  • EMBRYONIC STEM CELLS
  • Primitive (undifferentiated) cells, usually from
    the embryo, that have the potential to become a
    wide variety of specialized cell types.

16
Establishment of Human Embryonic Stem Cells
  • From spare IVF embryos
  • Therapeutic cloning, i.e. by somatic cell nuclear
    transfer
  • Induced pluripotent stem cells

17
Dominic Doyle
18
Bob Edwards and Patrick Steptoe
19
Over Three Million IVF and Thousands of PGD
Babies have been Born!
20

SEXUAL REPRODUCTION
21
HUMAN ES CELLS
First isolated in 1998 from spare blastocysts
donated by an In Vitro Fertilization
(IVF) program
22
Source NIH website Stem cells A Primer
23
CONCERN
  • Production of new human ES cells will involve the
    destruction of thousands of human embryos

24
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.

25
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.

26
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.

27
Establishment of Human Embryonic Stem Cells
  • From spare IVF embryos
  • Therapeutic cloning, i.e. by somatic cell nuclear
    transfer
  • Induced pluripotent stem cells

28
  • NUCLEAR TRANSPLANTATION TO PRODUCE STEM CELLS

29
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30
February 1997 Cloning of Dolly reported
31
Somatic Cell Nuclear Transfer Reproductive
Cloning
Sheep Cattle Goat Mule Pig Cat Mouse Rat Rabbit
32
ABILITY TO PRODUCE STEM CELLS GENETICALLY
IDENTICAL TO PATIENT
Day 5
Therapeutic
33
HOW DOES THIS RELATE TO HUMAN CLONING???
34
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35
CONCERN
  • NUCLEAR TRANSPLANTATION WILL BE
  • USED TO CLONE HUMAN BABIES.

36
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

37
CONCERN
  • Production of new human ES cells by somatic cell
    nuclear transfer will require an unlimited number
    of human oocytes from women donors

38
CONCERN
HUMAN EGG DONORS WILL BE EXPLOITED
Day 5
39
Establishment of Human Embryonic Stem Cells
  • From spare IVF embryos
  • Therapeutic cloning, i.e. by somatic cell nuclear
    transfer
  • Induced pluripotent stem cells

40
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
41
Images of iPPC picked at day 30
GFP-PFF
30
-1
0
2
3
20 O2
4 O2
42
Thank you
43
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?

44
ARE SUFFICIENT NUMBERS OF EMBRYONIC STEM CELL
LINES ADEQUATE FOR DEVELOPING THERAPIES?
45
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?
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