STEM CELLS: The Upside and
Downside of Stem Cell Science
Human ES cell colony: picture provided by
Dr. Toshihiko Ezashi
Stem
The main body or stalk of a plant
The stock of a family lineage
Specialized (differentiated) cells
Diploid, with 46 chromosomes
Haploid with 23 chromosomes
The human body consists of more than 10
trillion cells of more than 250 cell types
Neuronal stem cell
Bone marrow stem
cell
Skin stem cell
Intestinal stem cell
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 Applications 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?
UNIPOTENT STEM CELLS
M
N
H
P
Source: NIH website “Stem cells: A Primer”
ADULT 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 Cells
Niche Cells
Stem Cells
Progenitor cells
Precursor cells
Differentiated Cells
PLURIPOTENT (Adult)
STEM CELLS
Do such cells exist? Where?
Are they an alternative to
pluripotent embryonic stem
cells?
Source: NIH website “Stem cells: A Primer”
ADULT STEM CELLS
HAVE BROAD
THERAPEUTIC POTENTIAL (or do they?)
ADULT STEM CELLS
HAVE LIMITED
THERAPEUTIC POTENTIAL
Embryonic stem cells
What’s all the fuss about?
EMBRYONIC 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
Embryonic 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 Steptoe
Over Three Million IVF and
Thousands of PGD Babies have
been Born!
SEXUAL
REPRODUCTION
HUMAN ES CELLS
First isolated in 1998
from spare blastocysts donated by an
In Vitro Fertilization (IVF)
program
Source: NIH website “Stem cells: A Primer”
CONCERN
Production of new human ES cells will
involve the destruction of
thousands of human embryos
Facts
 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
EMBRYONIC STEM CELL LINES
ADEQUATE FOR DEVELOPING
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.
EMBRYONIC STEM CELLS
FOR THERAPY
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.
Establishment of Human
Embryonic Stem Cells
 From “spare” IVF embryos
 Therapeutic cloning, i.e. by somatic cell
nuclear transfer
 Induced pluripotent stem cells
NUCLEAR
TRANSPLANTATION TO
PRODUCE STEM CELLS
February 1997
Cloning of Dolly reported
Somatic Cell Nuclear Transfer
“Reproductive Cloning”
Sheep
Cattle
Goat
Mule
Pig
Cat
Mouse
Rat
Rabbit
ABILITY TO PRODUCE
STEM CELLS
GENETICALLY
IDENTICAL TO PATIENT
“Therapeutic
Day 5
HOW DOES THIS RELATE
TO HUMAN CLONING???
CONCERN
NUCLEAR TRANSPLANTATION
WILL BE
USED TO CLONE HUMAN BABIES.
NUCLEAR TRANSPLANTATION
TO PRODUCE 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
CONCERN
Production of new human ES cells by
somatic cell nuclear transfer will
require an unlimited number of
human oocytes from women donors
CONCERN
HUMAN EGG
DONORS
WILL BE EXPLOITED
Day 5
Establishment of Human
Embryonic 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
Takahashi (Yamanaka et al., Cell,2007
Yu (Thomson) et al. Science 2007
Lin28
Diagram from Zhares & Scholer, Cell 2007)
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
Images of iPPC picked at day 30
GFP-PFF
-1 0
2 3
4% O2
30
20% O2
Thank you
Issues
 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 NUMBERS
OF EMBRYONIC STEM CELL
LINES ADEQUATE FOR
DEVELOPING THERAPIES?
Some 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?