Download Stem Cells

Stem cell science and policy
By:
Rahul G. Thakar, Ph.D.
Wednesday June 20, 2007
Overview
• What are stem cells?
• Why use stem cells?
• Current application with
stem cells.
• Public policy regarding
stem cells.
Cells of the human body
• The human body is
composed of many
different types of cells
– e.g. muscle cells, skin cells,
liver cells, nerves,
cardiovascular cells, etc.
– Some are irreplaceable
• Not all cells have the same
potential
– Some cells remain
uncommitted - stem cells
– When stem cells differentiate,
they turn into the different
cells of the body
http://www.inventiveparent.com/Inside
Embryonic development
http://en.wikipedia.org/wiki/Image:StemCellsDia.png
In vitro fertilization - current method of deriving an
hESC line
• Eggs and sperm donated and fused to create a
fertilized egg in a petri dish
• Fertilized egg matures into a blastocyst
• Embryonic stem cells extracted from blastocyst
• Cells replated on another petri dish and grown in
culture
Embryonic development
What is a blastocyst?
• Trophoblast - a hollow sphere
of cells that develops into the
extra-embryonic membranes
such as the placenta, umbilical
cord, and amnion.
• Inner cell mass (ICM) embryonic stem cells are the
ICM
http://en.wikipedia.org/wiki/Image:Blastocyst.png
Special characteristics of ALL stem cells
• Self-renewal (proliferation)- the ability of a
stem cell to clone itself indefinitely by cell
division.
• Asymmetric cell division – more to come
• Relocation and Differentiation are abilities of
stem cells to “migrate” to where they’re
needed in the body and specialize into a
particular type of mature cell
Differentiation
Self-renew
a stem cell can reproduce
itself by cell division
Differentiate
a stem cell can specialize
into a particular type of
somatic cell
Stem cell division and differentiation
LEGEND
A - stem cell
B - progenitor cell
C - differentiated cell
1 - symmetric stem cell division
2 - asymmetric stem cell division
3 - progenitor division
4 - terminal differentiation
Generates every cell in the body including
the placenta and extra-embryonic tissues
Can form the entire human
being
Cannot form the entire
human being
Transdifferentiation?!
WHAT?
Can generate every cell in the body
except placenta and extra-embryonic
tissues
Become specific cell
types; may or may not
have plasticity
Adult stem cells
• Adult stem cells are cells
found in post-natal tissue
that can yield only the
specialized cell types of
the tissue from which they
originated.
–
–
–
–
hematopoietic stem cells
mesenchymal stem cells
umbilical cord stem cells
amniotic fluid stem cells
http://www.artsalive.ca/upload/dan/Articles_anatomy_full.jpg
Current adult stem cell therapies
Hematopoietic Stem Cell
Embryonic stem cells
• ESCs are derived from the inner cell mass of a
blastocyst
– Can self-renew indefinitely in culture
– ESCs used for research are made in a petri dish, not a
woman's body
– They hold great potential for alleviating the symptoms of
or even curing:
• Paralysis
• Diabetes
• Alzheimer’s
Mouse embryonic stem cells
What is stem cell research?
• Experimental model systems, understanding
more about development
• Cell-based therapies
• Pharmaceutical research and testing
Experimental model system - Cardiomyocytes
Cell-based therapySpinal Cord Injury
START
Clinical trials starting for treatment
of spinal cord injury* in humans
(after much data gathered using rats
as an animal model)
Differentiate
(+ growth factors)
time
Oligodendrocytes
markedly
recovered
injured
*Treatment may not work for the chronically paralyzed
Drug DevelopmentCancer Stem Cells
Reya, T., et al. Nature, 2001
Cell surface markers are a key difference.
Stem Cell Culture
Mouse feeder-layer
Artificially directing
stem cell fate
Why do you think this
is useful?
What problems do you
foresee in trying to
transplant this tissue
into a human?
Source: NIH
Somatic cell nuclear transfer
Directing stem cell differentiation
W.F. Liu, 2005
Tension can dictate differentiation
R. McBeath, 2004.
Substrate elasticity is a factor as well
A. Engler, 2006.
The deliciously malicious problem
R.G. Thakar, et. al, 2006
www.fda.gov/fdac/features/1999/attack.html
Coronary heart disease accounts for 36.3% deaths in the U.S. or 1 death every 36 seconds.
Traditional solutions
• Statin drugs, blood
thinning, beta-blockers,
ACE inhibitors,
angioplasty / stents
• These solutions are
worthwhile but do not
address the existing
damage to the
myocardium
http://www.nlm.nih.gov/medlineplus/ency/imagepages/17004.htm
Tissue engineering & the myocardium
• Approaches
– Chemical regulation
• Soluble chemical factors help
regulate growth, motility, and fate
• Deliver to site or evoke secretion
at the site
– Physical regulation
• Biomimetic materials
• Delivery of topographical cues to
promote attachment, alignment, and
contractilie phenotype
• Creation of an ordered, hierarchical
arrangement similar to in vivo
structures
C.M. Metallo, et al., Biotechnol. Prog., 23 (1),
18 -23, 2007.
Cell sources for the myocardium
• Smooth muscles cell, skeletal myoblasts,
endothelial progenitors
• Adult stem cells
• Embryonic stem cells
• Cardiac progenitors
D. Srivastava & K.N. Ivey Nature 441, 1097-1099(29 June 2006)
Our tangential studies
Orientation of neonatal cardiac myocytes grown
in 3D microrod-matrigel composite
Note myofibrils in finger–like projections attaching to microrod.
Also note all myofibrils are highly oriented.
Russell Lab
A
B
C
Morphology of neonatal myocytes. A:: NRVM in 3D gel only. B: increased
myocyte size with100μm microrods and gel. C: Note finger–like projections
from myocytes attaching to microrods. Actin in red, α-actinin in green, SU-8
microrods in blue.
Russell Lab
Stem cell policy
NIH’s role in federal policy
• On August 9th, 2001, President George W. Bush announced
that federal funds may be awarded for research using human
embryonic stem cells if the following criteria are met:
– The derivation process (which begins with the destruction of the
embryo) was initiated prior to 9:00 P.M. EDT on August 9, 2001.
– The stem cells must have been derived from an embryo that was
created for reproductive purposes and was no longer needed.
– Informed consent must have been obtained for the donation of the
embryo and that donation must not have involved financial
inducements.
Where it stands today
President Bush said in mid-May 2005, "I am a strong supporter of stem
cell research, but I've made it very clear to Congress that the use of
federal taxpayer money to promote science that destroys life in order to
save life, I am against this."
This was in response to the House and Senate passing versions of the
Stem Cell Resarch Enhancement Act of 2005. G.W. Bush vetoed the act
on July 19, 2006.
Again in 2007, the Senate of the new, 110th Congress passed bill S.5,
Stem Cell Research Enhancement Act of 2007. On June 7, 2007, the
House passed this legislation.
Acknowledgements
• Laurel Barchas
• George Gagnon
Questions