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8/3/2019 90.07.07A General Review on Stem Cells
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A General Review on
Stem Cells
Yu-Li Liu, Ph.D.
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What is Embryonic Stem Cells?
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Human Development
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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
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How long have embryonic
stem cells been studied?
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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 monkeysand marmosets.
JULY 1997 . cultured ESCs derived from primordial germ cells (taken fromaborted
fetuses) for seven months.
NOVEMBER 1998 .cultures of ESCs from human blastocysts
MARCH 1999 . FDA (UPDRS), the patient improves 4050 percent in certainmotor tasks, and his dopamine uptake increases 62 percent.
DECEMBER 1999 .Adult stem cells (ASCs), Science names stem cell researchthe Breakthrough of the Year.
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.
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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 notderivation of stem cells from human embryos.
JANUARY 2001 . President George W. Bush takes office.
JANUARY 17, 2001 .Bush receives a letter from 123 organizations asking him to allow HSC research tocontinue with federal support.
MARCH 15, 2001 . Deadline for submitting applications to the NIH for human ESC research projects.
APRIL 2001 .Stem Cell Research Act of 2001 allow federally funded researchers to derive ESCs independently.
APRIL 25, 2001 .Postpone Human Pluripotent Stem Cell Review Group (HPSCRG) until NIH guidelines havebeen reviewed.
JUNE 2001 . Expected announcement of reassessments of NIH guidelines regarding funding of humanpluripotent stem cell research.
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Embryonic Stem Cells and
Embryonic Germ Cells
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Where do human embryonic
stem cells come from?
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Human Embryonic Stem Cells
From in vitro fertilized embryos less
than a week old
These embryos were produced for
clinical purposes
No longer wanted for implantation
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Why are they important?
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Importance
Capability to develop into virtuallyany other cell
Possibility to grow into medicalimportant organs
bone marrow, neural tissue or muscle.
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How might they be used to
treat disease?
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Applications of Stem Cells
Growing tissues for transplantation
purposes
Treating disease because of defects inone of just a few cells types
Juvenile onset diabetes mellitus
Parkinson's disease
Replacing faulty cells with healthy ones
Failing hearts and other organs
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Are there other potential uses
for these cells?
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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
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Offer insights into cell
development
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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?
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No !!
They are not intact embryo
Fail to implant
Fail to develop into a fetus
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Is stem cell research the same
as cloning?
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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
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Why not using stem cells from
adults?
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Disadvantages in Adult Stem
Cells
Already specialized
Regenerate damaged tissue is very limited
Adults do not have stem cells in many vital
organs
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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 7:211-8 April 2001
Placenta
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Problems encountered for
cell-based therapy
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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
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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 therapy?
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Adult Stem Cells
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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 potentialofadulthuman
mesenchymalstemcells," Science, 284:143-7, April
2, 1999. (Citedin 145 papers)
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OrlicD.etal.Bonemarrowcellsregenerateinfarctedmyocardium.Nature.410 6829 :701-5 2001 A r 5.
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Bone marrow stem cells may repair
vital tissues and organs
A transplanted bone marrow stem cell can
not only reconstitute bone marrow, but alsomay play a role in healing these other
tissues and organs as well.
D.S. Krause et al. Multi-organ, multi-lineage
engraftment by a single bone marrow stem
cell. Cell, 105: 369-77 May 4, 2001
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Using mice pancreatic duct to
generate insulin-producingcells
Ramiya VK. Maraist M. Arfors KE.Schatz DA. Peck AB. Cornelius JG.
Reversal of insulin-dependent diabetes
using islets generated in vitro frompancreatic stem cells.
Nature Medicine. 6(3):278-82, 2000 Mar
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How to overcome the immune
rejection ?
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Differentiation of Embryonic
Stem Cell Lines Generated
from Adult Somatic Cells by
Nuclear Transfer
TeruhikoWakayama, VivianeTabar, Ivan
Rodriguez, AnthonyC. F.Perry, LorenzStuder,
andPeterMombaerts
Science Apr27 2001: 740-743.
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Somatic Cell Nuclear Transfer
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NT of Embryonic stem cells differentiated
into all kinds of tissues
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TeruhikoWakayama
University ofHawaii researcher
TeruhikoWakayama holds
cloned mice.
He is leaving after helpingdevelop the Honolulu
Technique, which enabled the
mice to be cloned.
His studies have utilized
microinjection techniques toanalyze the biology of
fertilization.
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How far should we go to reach
cell-based therapy ?
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Cellular replacement therapies for
neurological disorders
Human stem cell sources Source control
Eliminate HIV-positive donor
Records of cell preparation with donors and
patients 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
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Cellular replacement therapies for
neurological disorders
Manufacturing of stem cells
Do stem cells isolation and maintenance
procedures determine desirable cell fatesand preclude undesired cell fates?
Critical manufacturing process controls
Qualification of sources
Standard procedures to expand or maintain
stem cells
Development of validated tests to monitor the
stem cell identity and heterogeneity
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Cellular replacement therapies for
neurological disorders
Characterization of stem cell preparation andselection 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 correctfunctional phenotype expression
Markers to indicate adverse events Ectopic tissue differentiation, tumor genesis etc
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Cellular replacement therapies for
neurological disorders
Potency assays for stem cell products
Stem cell potency assays
Assessing intended bioactivity of stem cell
implants
Inter-assay variability
Dosage unit of potency be expected?
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TheFourthUS-Taiwan
NeuroscienceSymposium: Stem Cells, from cell level to
functional genomics
SanDiegoConventionCenter, SanDiego, CaliforniaNov. 10, 2001 (1:30 pmto 5:30 pm)
Asatellitesymposiumofthe 31stannualmeetingoftheSocietyforNeuroscienceoftheUnitedStates
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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 differentstem 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.
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TBA meeting Howstemcellsmakeabrain, andhowtofindthegenestheyuse
todoit. Derek van der Kooy, Ph.D. Professor, Cell Biology, Universityof Toronto, Toronto
Neuralstemcellsintheadultbrain: a perspectiveonneuropoiesis. Dennis A. Steindler, Ph.D. Professor, Neuroscience,University of Florida, Gainesville, FL
Neuralcreststemcells. David J. Anderson, Ph.D. Professor, Biology,and Howard Hughes Investigator, California Institute of Technology,
Pasadena, CA Plasticityofmultipotentstemcellsfromhumanbone
marrow. Catherine M. Verfaillie, M.D. Professor, Stem Cell Institute,University of Minnesota, Minneapolis, MN
Mesenchymalstemcellsinhomeostasisand pathogenesisofmaturearticularcartilage. Martin K. Lotz, M.D. Professor and Head,
Division of Arthritis Research, Scripps Research Institute, La Jolla, CA Geneand proteinexpressionwithmicroarray
technologies. Edison T. Liu, M.D. Director, Singapore GenomeProject, Republic of Singapore
Overviewonthefunctionalgenomics projectinTaiwan. Yuan-Tsong Chen, M.D., Ph.D. Professor & Chief, Medical Genetics, DukeUniversity Medical Center, Durham, NC
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Have a
Happy
Weekend !!
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