stem cells: the upside and downside of stem cell science human es cell colony: picture provided by...
TRANSCRIPT
STEM CELLS: The Upside STEM CELLS: The Upside and Downside of Stem Cell and Downside of Stem Cell
ScienceScience
Human ES cell colony: picture provided by Dr. Toshihiko Ezashi
StemStem
The main body or stalk of a plant
The stock of a family lineage
Specialized (differentiated) Specialized (differentiated) cellscells
Diploid, with 46 chromosomes
Haploid with 23 chromosomes
Skin stem cell
Neuronal stem cell
Intestinal stem cell
Bone marrow stem cell
The human body consists of more than The human body consists of more than 10 trillion cells of more than 250 cell 10 trillion cells of more than 250 cell
typestypes
What are stem cells?What are stem cells?
A stem cell has the ability to divide for indefinite number of divisions.
Stem cells give rise to more specialized cells when they differentiate.
There are three types of stem cell: unipotent, lineage specific stem cells, “adult” stem cells (multipotent), embryonic stem cells (pluripotent).
Real and Potential Real and Potential Applications of Stem CellsApplications of Stem Cells
Bone marrow transplantation Transplantation medicine (diabetes,
Parkinson’s Disease; stroke, arthritis, multiple sclerosis, heart failure; spinal cord lesions)
Drug testing Genetic change Other uses?
Source: NIH website “Stem cells: A Primer”
UNIPOTENT STEM CELLSUNIPOTENT STEM CELLS
M N H P
ADULT STEM CELLSADULT STEM CELLS
Undifferentiated, multipotent cells found in a differentiated tissue that can
renew themselves and (with certain limitations) differentiate to yield all the specialized cell types of the tissue from which it originated, e.g stem cells from bone marrow that can give rise to all
the blood cell types.
Stem Cells versus Progenitor Stem Cells versus Progenitor CellsCells
Niche Cells
Stem Cells
Progenitor cells
Differentiated Cells
Precursor cells
Source: NIH website “Stem cells: A Primer”
PLURIPOTENT (Adult) PLURIPOTENT (Adult) STEM CELLSSTEM CELLS
Do such cells exist? Where?
Are they an alternative to pluripotent embryonic stem cells?
ADULT STEM CELLSADULT STEM CELLS HAVE BROADHAVE BROAD
THERAPEUTIC POTENTIAL (or do THERAPEUTIC POTENTIAL (or do they?)they?)
ADULT STEM CELLSADULT STEM CELLS HAVE LIMITEDHAVE LIMITED
THERAPEUTIC POTENTIALTHERAPEUTIC POTENTIAL
Embryonic stem cellsEmbryonic stem cells
What’s all the fuss about?
EMBRYONIC STEM CELLSEMBRYONIC STEM CELLS
Primitive (undifferentiated) cells, usually from the embryo, that have
the potential to become a wide variety of specialized cell types.
Establishment of Human Establishment of Human Embryonic Stem CellsEmbryonic Stem Cells
From “spare” IVF embryos Therapeutic cloning, i.e. by somatic
cell nuclear transfer Induced pluripotent stem cells
Dominic Doyle
Bob Edwards and Patrick Bob Edwards and Patrick SteptoeSteptoe
Over Three Million IVF and Over Three Million IVF and Thousands of PGD Babies Thousands of PGD Babies
have been Born!have been Born!
SEXUALSEXUAL
REPRODUCTIONREPRODUCTION
HUMAN ES HUMAN ES CELLSCELLS
First isolated in 1998 from spare blastocysts donated by an
In Vitro Fertilization (IVF)program
Source: NIH website “Stem cells: A Primer”
CONCERNCONCERN
Production of new human ES cells will involve the destruction of thousands of human embryos
FactsFacts
Every year hundreds of thousands of human embryos are created by in vitro fertilization procedures designed to allow infertile couples to have children. To obtain eggs for IVF, eggs are produced by “superovulation” procedures
Many more eggs are produced and fertilized than can possibly be used.
Result: embryos are discarded or stored indefinitely.
ARE SUFFICIENT NUMBERS OF ARE SUFFICIENT NUMBERS OF EMBRYONIC STEM CELL LINES EMBRYONIC STEM CELL LINES ADEQUATE FOR DEVELOPING ADEQUATE FOR DEVELOPING
THERAPIES?THERAPIES? Different lines have different properties:
they don’t all behave the same. Existing stem cells will never be useful for
transplantation. Transplantation demands a close “match”
between the donor and the recipient, e.g. kidney transplantation. Hence there is a requirement for large numbers of cell lines with different transplantation antigens on their surfaces.
1.How to direct their differentiation efficiently into specific cell types (e.g. pancreas, brain neurons).
2. How to deliver them efficiently for tissue repair.
3. How to prevent immune rejection.
EMBRYONIC STEM EMBRYONIC STEM CELLS FOR THERAPYCELLS FOR THERAPY
Establishment of Human Establishment of Human Embryonic Stem CellsEmbryonic Stem Cells
From “spare” IVF embryos Therapeutic cloning, i.e. by somatic
cell nuclear transfer Induced pluripotent stem cells
NUCLEAR NUCLEAR TRANSPLANTATION TRANSPLANTATION TO PRODUCE STEM TO PRODUCE STEM
CELLSCELLS
February 1997February 1997 Cloning of Dolly reportedCloning of Dolly reported
Somatic Cell Nuclear Transfer Somatic Cell Nuclear Transfer “Reproductive Cloning”“Reproductive Cloning”
SheepCattleGoatMulePigCatMouseRatRabbit
Day 5
“Therapeutic
ABILITY TO PRODUCE ABILITY TO PRODUCE STEM CELLS STEM CELLS
GENETICALLYGENETICALLY
IDENTICAL TO PATIENTIDENTICAL TO PATIENT
HOW DOES THIS RELATE HOW DOES THIS RELATE TO HUMAN CLONING???TO HUMAN CLONING???
CONCERNCONCERN
NUCLEAR TRANSPLANTATION WILL BE
USED TO CLONE HUMAN BABIES.
NUCLEAR NUCLEAR TRANSPLANTATION TO TRANSPLANTATION TO PRODUCE STEM CELLSPRODUCE STEM CELLS
• NO EMBRYONIC OR FETAL DEVELOPMENT BEYOND 200 CELL STAGE (SIZE OF TIP OF PIN)
• NO TRANSFER TO UTERUS• BLASTOCYST OR STEM CELLS ALONE
CANNOT PRODUCE A NEW INDIVIDUAL
CONCERNCONCERN
Production of new human ES cells by somatic cell nuclear transfer will require an unlimited number of human oocytes from women
donors
Day 5
CONCERNCONCERN
HUMAN EGG HUMAN EGG DONORS DONORS
WILL BE EXPLOITEDWILL BE EXPLOITED
Establishment of Human Establishment of Human Embryonic Stem CellsEmbryonic Stem Cells
From “spare” IVF embryos Therapeutic cloning, i.e. by somatic
cell nuclear transfer Induced pluripotent stem cells
Pluripotent stem cells from adult fibroblasts
Nanog; Oct4 (POU domain transcription factor 5); Sox2, sex determining region Y-box 2 (SRY); Klf4 (Kruppel-like factor 4); c-Myc viral oncogene homolog; Lin28 homolog
Lin28Nanog
Takahashi (Yamanaka et al., Cell,2007Yu (Thomson) et al. Science 2007 Diagram from Zhares & Scholer, Cell 2007)
0 2 3-1
GFP-PFF
30
Images of iPPC picked at day 30
20% O24% O2
Thank you
IssuesIssues When does life begin? Missouri statutes
indicate that human life begins at the moment of conception
The new constitutional amendment and what it means
But the sperm and the egg are alive The transition from an embryo to a baby is a
gradual one Are embryos that cannot form a placenta or
that are doomed to die before the differentiation of the main organ systems individuals?
ARE SUFFICIENT ARE SUFFICIENT NUMBERS OF EMBRYONIC NUMBERS OF EMBRYONIC
STEM CELL LINES STEM CELL LINES ADEQUATE FOR ADEQUATE FOR
DEVELOPING THERAPIES?DEVELOPING THERAPIES?
Some QuestionsSome Questions
The status of hES cells. Are they the equivalent of embryos? Persons?
What are the objections to using spare embryos?
Are there alternatives to using hES cell lines for tissue replacement? Adult stem cells?
Can hES cells be produced by developing cell lines from a biopsy of an embryo?
Can embryos be created that lack any potential to develop into babies?