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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.

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Stem cell science and policy l.jpg

Stem cell science and policy

By:

Rahul G. Thakar, Ph.D.

Wednesday June 20, 2007


Overview l.jpg
Overview

  • What are stem cells?

  • Why use stem cells?

  • Current application with stem cells.

  • Public policy regarding stem cells.


Cells of the human body l.jpg
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 l.jpg
Embryonic development

http://en.wikipedia.org/wiki/Image:StemCellsDia.png


In vitro fertilization current method of deriving an hesc line l.jpg
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



What is a blastocyst l.jpg
What is a blastocyst? line

  • 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 l.jpg
Special characteristics of lineALL 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 l.jpg

Self-renew line

a stem cell can reproduce itself by cell division

Differentiate

a stem cell can specialize into a particular type of somatic cell

Differentiation


Stem cell division and differentiation l.jpg
Stem cell division and differentiation line

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


Slide11 l.jpg

Generates every cell in the body lineincluding the placenta and extra-embryonic tissues

Can form the entirehuman being

Can generate every cell in the body except placenta and extra-embryonic tissues

Cannot form the entire human being

Transdifferentiation?!

WHAT?

Become specific cell types; may or may not have plasticity


Adult stem cells l.jpg
Adult stem cells line

  • 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 l.jpg
Current adult stem cell therapies line

Hematopoietic Stem Cell


Embryonic stem cells l.jpg
Embryonic stem cells line

  • 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



What is stem cell research l.jpg
What is stem cell research? line

  • Experimental model systems, understanding more about development

  • Cell-based therapies

  • Pharmaceutical research and testing



Cell based therapy spinal cord injury l.jpg

START line

Cell-based therapy-Spinal Cord Injury

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 development cancer stem cells l.jpg

Reya, T., et al. lineNature, 2001

Drug Development-Cancer Stem Cells

Cell surface markers are a key difference.


Stem cell culture l.jpg
Stem Cell Culture line

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




Tension can dictate differentiation l.jpg
Tension can dictate differentiation line

R. McBeath, 2004.



The deliciously malicious problem l.jpg
The deliciously malicious problem line

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 l.jpg
Traditional solutions line

  • 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 l.jpg
Tissue engineering & the myocardium line

  • 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 l.jpg
Cell sources for the myocardium line

  • 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)



Orientation of neonatal cardiac myocytes grown in 3d microrod matrigel composite l.jpg
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


Slide31 l.jpg

A microrod-matrigel composite

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 l.jpg
Stem cell policy microrod-matrigel composite


Nih s role in federal policy l.jpg
NIH’s role in federal policy microrod-matrigel composite

  • 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 l.jpg
Where it stands today microrod-matrigel composite

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 l.jpg
Acknowledgements microrod-matrigel composite

  • Laurel Barchas

  • George Gagnon


Questions l.jpg
Questions microrod-matrigel composite


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