Title: STEM CELLS: The Upside and Downside of Stem Cell Science
1STEM CELLS The Upside and Downside of Stem Cell
Science
Human ES cell colony picture provided by Dr.
Toshihiko Ezashi
2Stem
- The main body or stalk of a plant
- The stock of a family lineage
3(No Transcript)
4Specialized (differentiated) cells
Diploid, with 46 chromosomes
Haploid with 23 chromosomes
5The human body consists of more than 10 trillion
cells of more than 250 cell types
6What 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).
7Real and Potential Applications of Stem Cells
- Bone marrow transplantation
- Transplantation medicine (diabetes, Parkinsons
Disease stroke, arthritis, multiple sclerosis,
heart failure spinal cord lesions) - Drug testing
- Genetic change
- Other uses?
8UNIPOTENT STEM CELLS
P
M
N
H
Source NIH website Stem cells A Primer
9- 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.
10Stem Cells versus Progenitor Cells
Niche Cells
Stem Cells
Progenitor cells
Precursor cells
Differentiated Cells
11PLURIPOTENT (Adult) STEM CELLS
Do such cells exist? Where? Are they an
alternative to pluripotent embryonic stem cells?
Source NIH website Stem cells A Primer
12ADULT STEM CELLS HAVE BROAD THERAPEUTIC
POTENTIAL (or do they?)
13ADULT STEM CELLS HAVE LIMITED THERAPEUTIC
POTENTIAL
14Embryonic stem cells
- Whats all the fuss about?
15- EMBRYONIC STEM CELLS
- Primitive (undifferentiated) cells, usually from
the embryo, that have the potential to become a
wide variety of specialized cell types.
16Establishment of Human Embryonic Stem Cells
- From spare IVF embryos
- Therapeutic cloning, i.e. by somatic cell nuclear
transfer - Induced pluripotent stem cells
17Dominic Doyle
18Bob Edwards and Patrick Steptoe
19Over Three Million IVF and Thousands of PGD
Babies have been Born!
20 SEXUAL REPRODUCTION
21HUMAN ES CELLS
First isolated in 1998 from spare blastocysts
donated by an In Vitro Fertilization
(IVF) program
22Source NIH website Stem cells A Primer
23CONCERN
- Production of new human ES cells will involve the
destruction of thousands of human embryos
24Facts
- 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.
25ARE SUFFICIENT NUMBERS OF EMBRYONIC STEM CELL
LINES ADEQUATE FOR DEVELOPING THERAPIES?
- Different lines have different properties they
dont 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.
26 EMBRYONIC STEM CELLS FOR THERAPY
- 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.
27Establishment of Human Embryonic Stem Cells
- From spare IVF embryos
- Therapeutic cloning, i.e. by somatic cell nuclear
transfer - Induced pluripotent stem cells
28- NUCLEAR TRANSPLANTATION TO PRODUCE STEM CELLS
29(No Transcript)
30February 1997 Cloning of Dolly reported
31 Somatic Cell Nuclear Transfer Reproductive
Cloning
Sheep Cattle Goat Mule Pig Cat Mouse Rat Rabbit
32ABILITY TO PRODUCE STEM CELLS GENETICALLY
IDENTICAL TO PATIENT
Day 5
Therapeutic
33HOW DOES THIS RELATE TO HUMAN CLONING???
34(No Transcript)
35CONCERN
- NUCLEAR TRANSPLANTATION WILL BE
- USED TO CLONE HUMAN BABIES.
36NUCLEAR 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
37CONCERN
- Production of new human ES cells by somatic cell
nuclear transfer will require an unlimited number
of human oocytes from women donors
38CONCERN
HUMAN EGG DONORS WILL BE EXPLOITED
Day 5
39Establishment of Human Embryonic Stem Cells
- From spare IVF embryos
- Therapeutic cloning, i.e. by somatic cell nuclear
transfer - Induced pluripotent stem cells
40Pluripotent stem cells from adult fibroblasts
Lin28
Nanog
Takahashi (Yamanaka et al., Cell,2007 Yu
(Thomson) et al. Science 2007
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
41Images of iPPC picked at day 30
GFP-PFF
30
-1
0
2
3
20 O2
4 O2
42Thank you
43Issues
- 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?
44ARE SUFFICIENT NUMBERS OF EMBRYONIC STEM CELL
LINES ADEQUATE FOR DEVELOPING THERAPIES?
45Some 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?