90.07.07A General Review on Stem Cells

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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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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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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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 !!

Documents

90.07.07A General Review on Stem Cells