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A General Review on Stem Cells


JANUARY 31, 2000 .Stem Cell Research Act of 2000. AUGUST 25, 2000 .NIH Guidelines for Research Using Human Pluripotent Stem Cells, ... – PowerPoint PPT presentation

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Title: A General Review on Stem Cells

A General Review on Stem Cells
  • Yu-Li Liu, Ph.D.

What is Embryonic Stem Cells?
Human Development
Embryonic Stem Cells
  • Derived from the inner cell mass of an
    early-stage embryo
  • Undifferentiated cells
  • Unlike any specific adult cell
  • Ability to form any adult cell
  • Proliferate indefinitely in culture
  • An unlimited source of specific, clinically
    important adult cells
  • Bone, muscle, liver, neural, gut, or blood cells

How long have embryonic stem cells been studied?
A science and political issue
  • 1981 . culture mouse ESCs.
  • 1986 . mouse knockout technology.
  • 1992 . discovery of embryonic germ (EG) cells.
  • 1996 . ESCs made from pigs, cows, rabbits, and
    sheep, from rhesus monkeys and marmosets.
  • JULY 1997 . cultured ESCs derived from primordial
    germ cells (taken from aborted
  • fetuses) for seven months.
  • NOVEMBER 1998 .cultures of ESCs from human
  • MARCH 1999 . FDA (UPDRS), the patient improves
    4050 percent in certain motor tasks, and his
    dopamine uptake increases 62 percent.
  • DECEMBER 1999 .Adult stem cells (ASCs), Science
    names stem cell research the Breakthrough of the
  • JUNE 2000 .ASCs turns skeletal muscle stem cells
    into blood cells.
  • AUGUST 2000 . Identify progenitor cells in hair
    follicle in mice.
  • OCTOBER 2000 . Nature Neuroscience publishes
    findings that neural ASCs can be directed to
    differentiate into skeletal muscle cells.
  • JANUARY 31, 2000 .Stem Cell Research Act of 2000.
  • AUGUST 25, 2000 .NIH Guidelines for Research
    Using Human Pluripotent Stem Cells, which permit
    use but not derivation of stem cells from human
  • JANUARY 2001 . President George W. Bush takes
  • JANUARY 17, 2001 .Bush receives a letter from 123
    organizations asking him to allow HSC research to
    continue with federal support.
  • MARCH 15, 2001 . Deadline for submitting
    applications to the NIH for human ESC research
  • APRIL 2001 .Stem Cell Research Act of 2001 allow
    federally funded researchers to derive ESCs
  • APRIL 25, 2001 .Postpone Human Pluripotent Stem
    Cell Review Group (HPSCRG) until NIH guidelines
    have been reviewed.
  • JUNE 2001 . Expected announcement of
    reassessments of NIH guidelines regarding funding
    of human pluripotent stem cell research. 

Embryonic Stem Cells and Embryonic Germ Cells
Where do human embryonic stem cells come from?
Human Embryonic Stem Cells
  • From in vitro fertilized embryos less than a week
  • These embryos were produced for clinical purposes
  • No longer wanted for implantation

Why are they important?
  • Capability to develop into virtually any other
  • Possibility to grow into medical important organs
  • bone marrow, neural tissue or muscle.

How might they be used to treat disease?
Applications of Stem Cells
  • Growing tissues for transplantation purposes
  • Treating disease because of defects in one of
    just a few cells types
  • Juvenile onset diabetes mellitus
  • Parkinson's disease
  • Replacing faulty cells with healthy ones
  • Failing hearts and other organs

Are there other potential uses for these cells?
Other Potential Applications
  • Drug discovery
  • New medications could be initially tested using
    human stem cell lines.
  • This would not replace testing in whole animals
    and testing in human beings, but it would
    streamline the process of drug development.
  • Permit the rapid screening of hundreds of
    thousands of chemicals

Offer insights into cell development
  • Human development have been difficult or
    impossible to study
  • Offer opportunities to study developmental events
    in humans in utero
  • Preventing or treating birth defects, infertility
    and pregnancy loss
  • Reduce the risk of drug-related birth defects.

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If these cells were transferred to a woman, could
a pregnancy result?
No !!
  • They are not intact embryo
  • Fail to implant
  • Fail to develop into a fetus

Is stem cell research the same as cloning?
Goals in Stem Cell Research
  • Develop new life-saving treatments
  • Cannot be used to develop a human being
  • Embryonic stem cells cannot give rise to a
    placenta, so a human being could not develop,
    even if the stem cells were implanted into a
    woman's uterus

Why not using stem cells from adults?
Disadvantages in Adult Stem Cells
  • Already specialized
  • Regenerate damaged tissue is very limited
  • Adults do not have stem cells in many vital organs

Human tissues harbored adult stem cells
  • Skin
  • Neurons
  • Adipose
  • P.A. Zuk et al Multilineage cells from human
    adipose tissue implications for cell-based
    therapies. Tissue Engineering 7211-8 April 2001
  • Placenta

Problems encountered for cell-based therapy
Technical Problems
  • This research is still in its infancy
  • How to control the differentiation of stem cells
    so they will be therapeutically effective ?
  • Study the potential of immune rejection of the
    cells, and how to overcome that problem

Stem Cell Therapy
  • Therapeutic cloning
  • involves growing replacement organs (heart,
    liver, pancreas, skin, etc) from a sample of a
    patients DNA.
  • Cellular reprogramming
  • Fuse patients DNA with embryonic germ cells

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Does adult stem cell serve less in cell-based
Adult Stem Cells
Multilineage potential of adult human mesenchymal
stem cells
  • M.F. Pittenger, A.M. Mackay, S.C. Beck, R.K.
    Jaiswal, R. Douglas, J.D. Mosca, M.A. Moorman,
    D.W. Simonetti, S. Craig, D.R. Marshak,
    "Multilineage potential of adult human
    mesenchymal stem cells," Science, 284143-7,
    April 2, 1999. (Cited in 145 papers)

Orlic D. et al. Bone marrow cells regenerate
infarcted myocardium. Nature. 410(6829)701-5,
2001 Apr 5.
Bone marrow stem cells may repair vital tissues
and organs
  • A transplanted bone marrow stem cell can not only
    reconstitute bone marrow, but also may play a
    role in healing these other tissues and organs as
  • D.S. Krause et al. Multi-organ, multi-lineage
    engraftment by a single bone marrow stem cell.
    Cell, 105 369-77 May 4, 2001

Using mice pancreatic duct to generate
insulin-producing cells
  • Ramiya VK. Maraist M. Arfors KE. Schatz DA. Peck
    AB. Cornelius JG. Reversal of insulin-dependent
    diabetes using islets generated in vitro from
    pancreatic stem cells.
  • Nature Medicine. 6(3)278-82, 2000 Mar

How to overcome the immune rejection ?
Differentiation of Embryonic Stem Cell Lines
Generated from Adult Somatic Cells by Nuclear

Teruhiko Wakayama, Viviane Tabar, Ivan Rodriguez,
Anthony C. F. Perry, Lorenz Studer, and Peter
Mombaerts Science Apr 27 2001 740-743.
Somatic Cell Nuclear Transfer
NT of Embryonic stem cells differentiated into
all kinds of tissues
Teruhiko Wakayama
  • University of Hawaii researcher Teruhiko Wakayama
    holds cloned mice. He is leaving after helping
    develop the Honolulu Technique, which enabled
    the mice to be cloned.
  • His studies have utilized microinjection
    techniques to analyze the biology of

How far should we go to reach cell-based therapy
Cellular replacement therapies for neurological
  • Human stem cell sources
  • Source control
  • Eliminate HIV-positive donor
  • Records of cell preparation with donors and
  • What record should be kept?
  • Who could access to them?
  • How long should records be maintained?
  • IF tissue origin is not traceable
  • Stem cell source qualification
  • Should genetic markers be evaluated?
  • Are genetic tests sufficient and reliable?
  • Source of derivation
  • Autologous donation, allogeneic donation,
    embryonic stem cells or embryonic germ cells

Cellular replacement therapies for neurological
  • Manufacturing of stem cells
  • Do stem cells isolation and maintenance
    procedures determine desirable cell fates and
    preclude undesired cell fates?
  • Critical manufacturing process controls
  • Qualification of sources
  • Standard procedures to expand or maintain stem
  • Development of validated tests to monitor the
    stem cell identity and heterogeneity

Cellular replacement therapies for neurological
  • Characterization of stem cell preparation and
    selection of specifications
  • Heterogeneous cell populations
  • Essential to intended effect, some deleterious,
    and some inert
  • Purity specification
  • Markers to identify cell phenotype, determination
    or fate
  • Markers necessary to ensure correct functional
    phenotype expression
  • Markers to indicate adverse events
  • Ectopic tissue differentiation, tumor genesis etc

Cellular replacement therapies for neurological
  • Potency assays for stem cell products
  • Stem cell potency assays
  • Assessing intended bioactivity of stem cell
  • Inter-assay variability
  • Dosage unit of potency be expected?

The Fourth US-Taiwan Neuroscience Symposium
  • Stem Cells, from cell level to functional
    genomics San Diego Convention Center, San Diego,
    California Nov. 10, 2001 (130 pm to 530 pm)
  • A satellite symposium of the 31st annual meeting
    of the Society for Neuroscience of the United

TBA meeting
  • This symposium of Taiwanese Bioscientists of
    America (TBA) highlights recent advances in stem
    cell research, focusing on the functional and
    phenotypic analysis of different stem cells and
    their plasticity for multiple potentialities. The
    symposium program includes four major themes
  • (1) neural stem cells,
  • (2) mesenchymal stem cells,
  • (3) embryonic stem cells, and
  • (4) functional genomic analysis.

TBA meeting
  • How stem cells make a brain, and how to find the
    genes they use to do it.  Derek van der Kooy,
    Ph.D. Professor, Cell Biology, University of
    Toronto, Toronto
  • Neural stem cells in the adult brain a
    perspective on neuropoiesis.  Dennis A.
    Steindler, Ph.D. Professor, Neuroscience,
    University of Florida, Gainesville, FL
  • Neural crest stem cells.  David J. Anderson,
    Ph.D. Professor, Biology, and Howard Hughes
    Investigator, California Institute of Technology,
    Pasadena, CA
  • Plasticity of multipotent stem cells from human
    bone marrow.  Catherine M. Verfaillie, M.D.
    Professor, Stem Cell Institute, University of
    Minnesota, Minneapolis, MN
  • Mesenchymal stem cells in homeostasis and
    pathogenesis of mature articular cartilage. 
    Martin K. Lotz, M.D. Professor and Head, Division
    of Arthritis Research, Scripps Research
    Institute, La Jolla, CA
  • Gene and protein expression with microarray
    technologies.  Edison T. Liu, M.D. Director,
    Singapore Genome Project, Republic of Singapore
  • Overview on the functional genomics project in
    Taiwan.  Yuan-Tsong Chen, M.D., Ph.D. Professor
    Chief, Medical Genetics, Duke University Medical
    Center, Durham, NC

Have a Happy Weekend !!
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