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The Future for Stem Cell Research

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The Future for Stem Cell Research. Robin Lovell-Badge ... Embryonic stem cells ' stem cells are the newest 'hot' topic in biological research ' ... – PowerPoint PPT presentation

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Title: The Future for Stem Cell Research


1
The Future for Stem Cell Research
  • Robin Lovell-Badge
  • Division of Developmental Genetics, MRC National
    Institute for Medical Research
  • Nature 2001 414 88-91
  • 2001. 11. 16
  • Park, Ji-Yoon

2
Contents
  • 1. Introduction
  • 2. Background
  • A. What are Stem Cells?
  • B. Properties of Human ES Cells
  • 3. Where do embryonic stem cells come from?
  • 4. Why are embryonic stem cells important?
  • 5. How might embryonic stem cells be used to
    treat disease?
  • 6. Why not derive stem cells from adults?
  • 7. What are the benefits of studying embryonic
    stem cells?

3
What are embryonic stem cells?
  • Embryonic stem cells
  • stem cells are the newest "hot" topic in
    biological research
  • are undifferentiated cells that are
    unlike adult cell
  • have the ability to choose between
    prolonged self-renewal differentiation
  • fate choice highly regulated by
    intrinsic signals the external environment
  • only found naturally in the early stages
    of embryonic development and are totipotent
  • they have the ability to form any adult
    cell
  • - undifferentiated embryonic stem cells
    can proliferate indefinitely in culture
  • - they could potentially provide an
    unlimited source of specific, clinically
    important adult cells
  • such as bone, muscle, liver or blood
    cell

4
Properties of Human ES Cells
  • Relatively flat, compact colonies that easily
    dissociate into single cells in trypsin or in
    Ca2 - and Mg2 - free medium
  • Grow more slowly than mouse ES cells
  • Population-doubling time 36 hrs , / mouse ES
    cells 12hrs
  • In vitro culture requirements for
    undifferentiated growth
  • mouse - LIF(leukemia inhibitory factor)
  • human - feeder layers serum / or
    serum-free media, bFGF
  • fibroblast feeder layers prevent
    differentiation of human ES cells
  • Remarkably stable karyotypes
  • normal XX and XY karyotype
  • model of the study of developmental
    biology mechanism
  • Expression of high levels of telomerase
  • maintain their length, is highly
    correlated with immortality in human cell line

5
Where do embryonic stem cells come from?
  • Human embryonic stem cells
  • are derived from fertilized embryos
    less than a week old
  • using 14 blastocysts obtained from
    donated, surplus embryos produced
  • by in vitro fertilization
  • James Thomson established five
    independent stem cell lines in November
  • 1998
  • This was the first time human
    embryonic stem cells had been successfully
  • isolated and cultured
  • The cell lines
  • capable of prolonged,
    undifferentiated proliferation in culture
  • maintained the ability to develop
    into a variety of specific cell types,
  • including neural, gut, muscle, bone
    and cartilage cells.

6
Why are embryonic stem cells important?
  • Drug discovery
  • The ability to grow pure populations
    of specific cell types
  • - offers a proving ground for
    chemical compounds that may have medical
    importance
  • - treating specific cell types with
    chemicals and measuring their response offers a
  • short-cut to sort out chemicals
    that can be used to treat the diseases
  • - would permit the rapid screening of
    hundreds of thousands of chemicals that must
  • now be tested through much more
    time-consuming processes
  • Benefits
  • offer insights into developmental
    events that cannot be studied directly in humans
    in
  • utero or fully understood through
    the use of animal models
  • knowledge of normal development could
    ultimately allow the prevention or treatment
  • of abnormal human development

7
How might embryonic stem cells be used to treat
disease?
  • The ability to grow human tissue of all kinds
    opens the door to treating a range of cell-based
    diseases and to growing medically important
    tissues that can be used for transplantation
    purposes.

8
Why not derive stem cells from adults?
  • There are several approaches now in human
    clinical trials that utilize mature stem cells
    (such as blood-forming cells, neuron-forming
    cells and cartilage-forming cells)
  • because adult cells are already specialized,
    their potential to regenerate damaged tissue is
    very limited
  • Adults do not have stem cells in many vital
    organs, so when those tissues are damaged, scar
    tissue develops. Only embryonic stem cells, which
    have the capacity to become any kind of human
    tissue, have the potential to repair vital
    organs.
  • adult stem cells are difficult to grow in the lab
    and their poetntial to reproduce diminishes with
    age.
  • Studies of adult stem cells are important and
    will provide valuable insights into the use of
    stem cell in transplantation procedures.

9
What are the benefits of studying embryonic stem
cells?
  • They have the potential to treat or cure a myriad
    of diseases, including Parkinson's, Alzheimer's,
    diabetes, heart disease, stroke, spinal cord
    injuries and burns.
  • Understand what leads cells to specialization in
    order to direct cells to become particular types
    of tissue.
  • To study the potential of immune rejection of the
    cells, and how to overcome that problem.

10
Derivation of human ES cell lines
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15
In vitro differentiation of human ES cells under
a variety of conditions
16
Pluripotency of mouse embryonic stem (ES) cells
  • Fig 1.a, Aggregates of mouse ES cells forming
    embryoid bodies. The dark staining shows
    expression of Sox2 in the less differentiated
    cells, whereas the rind of differentiated
    endoderm is unstained. (Image courtesy of A.
    Avilion).
  • b, Histological section of a teratocarcinoma
    derived from mouse ES cells. Many different cell
    types are found, all formed from the ES cells,
    including representatives of all three germ
    layers. (Image courtesy of M. Parsons.) c, The
    ultimate test of pluripotentiality a chimaera
    made by injecting ES cells into a blastocyst. The
    pigmented areas reveal the contribution of ES
    cell derivatives to the skin, but all tissues are
    composed of a mixture of ES and host embryo
    derivatives. Even a single ES cell can give a
    chimaera like this.

17
Fig 2. A small primary neurosphere, obtained from
one or a few cells from the dorsal telencephalon
of a 14.5-d.p.c. mouse embryo, which has been
grown in culture for 21 days. This is stained
with DAPI (blue) to reveal nuclei and with both
SOX2 (green) and Nestin (red) to reveal neural
progenitor cells. Many, if not all, of these
cells have properties of neural stem cells.
(Figure courtesy of E. Remboutsika.)
18
Tissue derivatives of all three EG layers
differentiated from human ES cells in vivo
19
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20
Definition
  • Somatic cell - cell of the body other than egg or
    sperm.
  • Somatic cell nuclear transfer
  • - the transfer of a cell nucleus from a
    somatic cell into an egg from which the
  • nucleus has been removed.
  • Stem cells
  • - cells that have the ability to divide
    for indefinite periods in culture and to
  • give rise to specialized cells.
  • Pluripotent
  • - capable of giving rise to most tissues
    of an organism.
  • Totipotent
  • - having unlimited capability. Totipotent
    cells have the capacity to specialize
  • into extraembryonic membranes and
    tissues, the embryo, and all postembryonic
  • tissues and organs.
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