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Stem Cells: Scientific Potential and Alternatives

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Stem Cells: Scientific Potential and Alternatives Glenn Sauer, Ph.D. Biology Department Fairfield University Scientific Principles What are stem cells? – PowerPoint PPT presentation

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Title: Stem Cells: Scientific Potential and Alternatives


1
Stem Cells Scientific Potential and Alternatives
  • Glenn Sauer, Ph.D.
  • Biology Department
  • Fairfield University

2
Scientific Principles
  • What are stem cells?
  • How are they used?
  • What is the potential for therapeutic
    applications?
  • More information
  • www.nih.gov

3
Review of Terminology
  • DNA - deoxyribonucleic acid, makes up genes
  • Gene - functional unit of heredity, a segment of
    DNA located at a specific site on a chromosome
    genes direct the formation of proteins.
  • Nucleus - a membrane bound structure in the cell
    which contains the chromosomes.
  • Cell - the basic unit of life, all living
    organisms are made up of cells
  • somatic cell - a cell of the body (220 types in
    humans)
  • germ cell - an egg or sperm

4
Differentiation of Human Tissues
  • Early embryonic cells unspecialized
  • Three primary tissue layers
  • Ectoderm
  • Mesoderm
  • Endoderm
  • All tissues develop from here

5
Adult Stem Cells
  • Stem cells cells that have the ability to
    divide for indefinite periods and give rise to
    specialized cells
  • Progenitor cells partially specialized cells
    that can give rise to particular cell types

6
Stem Cells of the Bone Marrow
7
The Problem of Cell Potency
  • Unipotent - cell divides to produce same cell
    type most cells
  • Multipotent - can give rise to some cell types
    adult stem cells
  • Pluripotent - able to give rise to most cell
    types embryonic, very small number of adult stem
    cells
  • Totipotent - unlimited cabability can give rise
    to all cell types only in early embryos

8
Early Embryological Development
9
Derivation of Human Pluripotent Stem Cells
  • John Gearhart (1998) - embryonic germ (EG) cells
    cultured from gonadal ridge of 5- to 9-week old
    fetal tissue obtained from elective abortions.
    Proc. Natl. Acad. Sci. USA 95 13726-13731.
  • James Thomson (1998) - embryonic stem (ES) cells
    derived from inner cell mass of blastocysts
    created through in vitro fertilization procedures
    and donated for research purposes.
    Science 282 1145-1147.

10
Derivation of hES Cells
  • Excess frozen blastocysts donated from
    fertility clinics
  • Inner cell mass (embryo) separated from
    trophoblast (placenta)
  • Cells dissociated and cultured in laboratory
  • Can be made to differentiate using chemical
    signals

11
Applications of Pluripotent Stem Cells
  • Basic research in human development
  • decision-making genes (birth defects, cancer)
  • Drug development
  • human cell lines for all cell types
  • Cell therapies
  • replacement tissue for degenerative conditions
    (Parkinsons and Alzheimers disease, diabetes,
    heart disease, stroke, arthritis)

12
Example Diabetes
  • Insufficient insulin production in pancreas
  • Insulin needed for glucose uptake
  • Islet-like cells derived from stem cells
    produce insulin
  • Eliminates need for insulin injections

13
Scientific Challenges Remaining
  • Understanding of cellular events that lead to
    differentiation and specialization
  • Immunologic rejection - Can stem cells be
    modified to minimize tissue incompatibility?
  • Time of development and expense of treatments

14
Rejection Possible Solutions
  • Genetic engineering
  • Somatic cell nuclear transfer (SCNT)
  • develops into a blastocyst
  • Dolly the sheep
  • cloning (banned by Congress)

15
The Controversy
  • Tremendous potential
  • scientific community
  • medical profession
  • patient advocates
  • Religious/ethical conflict
  • human dignity
  • abortion issue

16
When does Human Life Begin?
  • Genetic view - at conception (fertilization)
  • Embryologic view - after 14 days when each embryo
    can produce only one individual
  • Mental activity view - after 25 weeks when the
    human-specific EEG can be measured (death is
    defined as the loss of EEG)
  • Birthday view - life begins when infant is
    metabolically independent of mother

17
The Bush Decision - Aug 9, 2001
  • We must proceed with great care - limited
    approval for ongoing research.
  • Fully funded adult stem cells, umbilical cord
  • Restricted embryonic (existing cell lines only)
  • 64 existing lines
  • 20 in United States
  • Sweden, India, Australia, Israel
  • Unfunded new donor embryos, cloned embryos
  • Total federal funding for 2001 250 M

18
Reaction to Bush Decision
  • Scientists
  • some better than none
  • 64 cell lines not enough
  • concerns about control
  • Conservative Christians
  • relief that more research is not allowed
  • broken campaign promise
  • Patient Advocates
  • cautious optimism
  • emotional pleas for more

19
Religions Ponder the Issue
  • Roman Catholic, Evangelical Christians - opposed
    since stem cells are derived from the destruction
    of embryos
  • Most groups do not have official positions
  • Most common positions
  • Judaism - supportive since it serves a common
    good (fighting disease)
  • Muslim - abortion is wrong but life begins when
    fertilized egg touches womb
  • Presbyterian, UCC - generally supportive

20
State Response
  • California voters approve Proposition 71 which
    provides 3 Billion for stem cell research (2004)
  • Other states approve similar measures
    (Connecticut, Florida, Illinois, Massachusetts,
    Missouri, New Hampshire, New York, Pennsylvania,
    Texas, Washington, Wisconsin)

21
Stem Cell Research Enhancement Act
  • Would allow use of surplus in vitro fertilization
    embryos with donor permission (2005)
  • Passed House of Representatives (238-194) and
    Senate (63-37)
  • Vetoed by George Bush (2006)
  • Stem Cell Therapeutic and Research Act of 2005
    (enacted)
  • Provides funds for adult stem cell therapies and
    umbilical cord stem cells

22
Current Situation
  • Barack Obama executive order allows research with
    new stem cell lines (2009)
  • BUT Dickey Amendment to 1995 Appropriations Bill
    bans funds for human cloning or any research that
    voluntarily destroys embryos.
  • RESULT ? Research Labs using state funds to
    create stem cell lines and federal funds to work
    with the cells

23
Alternatives to hES Cells
  • Umbilical cord blood
  • Contains hematopoietic and mesenchymal stem cells
    (lower potency than hES)
  • Patient specific
  • Cord blood banks
  • 2000 collection and 125/year storage fees
  • Some public banks for donated cells

24
Alternatives to hES Cells
  • Induced Pluripotent Stem Cells (iPS)

25
Alternatives to hES Cells
  • Induced Pluripotent Stem Cells (iPS)
  • Uses Oct4, Sox2, Klf4 and c-Myc genes
  • Show higher potency than cord cells
  • Low efficiency (recent improvements)
  • Other problems
  • Abnormal aging
  • Tumor production
  • Incomplete reprogramming

26
Alternatives to hES Cells
  • Direct Cell Reprogramming - 2011
  • Turns one cell directly into another
  • (ex. Skin cell ? Neuron)
  • Uses mRNA, no viral vector
  • Eliminates need for stem cells
  • Potential and problems are uncertain

27
Autologous Stem Cell Therapies
  • Self-donation of mesenchymal stem cells
  • Injected (with or without chemical treatment)
    into injury site
  • Not FDA approved
  • Clinical trials underway (heart attack, spinal
    cord injury, etc.)
  • Many Americans seek overseas options
  • No proven effectiveness
  • Costly
  • High pressure sales tactics

28
Questions?
  • The United States has been criticized by some for
    being too restrictive to stem cell-based research
    and therapies. Should U.S. laws be relaxed to be
    more accommodating to those wishing treatment?
  • A recent study by Duke University predicted that
    by the year 2050, regenerative procedures based
    on stem cell and other biotechnologies could
    extend an average human life span by up to 100
    years. Is this a desirable goal?
  • Many biotechnologies are vastly expensive, yet
    much of the basic research supporting these
    developments is paid for by taxpayers. Who
    should benefit?
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