jim wells, ph.d assistant professor division of developmental biology children’s hospital research...
TRANSCRIPT
Jim Wells, Ph.D
Assistant Professor
Division of Developmental Biology
Children’s Hospital
Research Foundation of Cincinnati
513-636-8767
Stem cell potential
Google“Hits”
(x 1,000,000)
1
0.5
August2005
200420032002
Google search for “human stem cell ethics”
2700%increase
(~10% type 1)
Stem cells
Pluripotentembryonicstem cells
PSCs
Adultstem cells
Also cord blood stem cells
Goal of all stem cell research
Cure disease
Adultstemcells
stem cellPSC/ES cells
in vitro
MakeTherapeuticCells in vitro
(in a petri dish)
Therapeuticcell
Source of pluripotent/embryonic stem cells
Human embryo 4 days after
in vitro fertilization
~20 cells
Eye of a needle
0.1mm4/1000th
inch
Making pluripotent Stem Cell lines
Donated surpluseggs from IVF clinics
Cells will grow Indefinitely in
a petri dish
Make billions of copies
Limitless supply of Potential therapeutic
cells* KeepFrozen
Otheroptions
Discard as medical
waste
* It is esimated that 400,000 surplus eggs are stored/frozen in the US
Cell Line
Pluripotent Stem Cell lines
Cell line 1
Wisconsin
Göteborg
Haifa
Cell line 2
Cell line 3
Examples of what PSCs can become
Potential limitless supply of any diseased cell
Heartcells
Bonecells
GutcellsBrain
neurons
Spinalcord
neurons
Skincells
Bloodcells
Musclecells
(Crohne’s disease)
(Oteoporosis)
(MuscularDystrophy)
(Cardiovasculardisease)
(Anemia,Cancer)
(Burns)
(Paralysis)
(Alzheimer’sMultipleSclerosis)
-cells(Diabetes)
~50,000,000,000,000 total cells
Skin stem cells
Blood stem cells
No adult stem cell for -cells in vivo X
Examples of Adult stem cells
Muscle stem cells
?
Comparison of stem cells
Human adult SC’s
Human PSC’s
• First isolated in November, 1998
• Pluripotent - can become all celltypes of the body
• Can multiply indefinitely in vitro
• Un-tested therapeutically
• First identified 4 decades ago
• Multipotent - can become some cell types of the body
• Limited replication in vitro
• Some therapeutics available
Future stem cell therapeutics
Human adult SC’s
Human PSC’s • Diabetes• Alzheimer’s• Stroke• Cardiovascular disease• Autoimmune disease• Parkinson’s• Cancer• Burns• Spinal chord injury• Birth defects
?
?
Human adult SC’s
• Alzheimer’s
• Cardiovascular disease
• Cancer• Burns• Spinal chord injury
Future stem cell therapeutics
?
Human PSC’s • Diabetes
• Stroke
• Autoimmune disease• Parkinson’s
• Birth defects
Future stem cell therapeutics
?
Future stem cell potential
We don’t yet know which type ofstem cell will ultimately cure
these different diseases
Approved pluripotent Stem Cell lines
Cell line 1
Wisconsin
Göteborg
Haifa
Cell line 2
Cell line 3
There are between 11 and 20 approved lines availableat the stem cell registry at the National Institutes of Health.
Developed before August 2001
Current stem cell lines have limited therapeutic potential because:
1. Significant differences exist between cell lines
2. Grown with mouse cells as “feeders”
3. Little genetic diversity
4. Corporate funding/proprietary issues
5. Excludes use of patient-specific cell lines
1. Significant differences between cell lines
• Physically different
• Genetically different/chromosomal abnormalities
• Multiply differently
• Differences in their ability to become therapeutic cell types?
Are these differences important?
Wisconsin
Göteborg
Haifa
Different lines may have different therapeutic potential, or none at all
Hundreds of different cell types in the body affected by disease
NOTHING
-cells
nerves
?
?
?
2. Human PSCs grown with mouse cells
Feeder mouse cells provide important nutrients to help PSCs grow
ALL existing cell lines were originally grown with mouse cells
Possibility that mouse pathogens/viruses contaminate all cell lines
Scientists have recently learned how to grow PSCs on human cells
New “mouse free” cell lines have become available but are unapproved
Mouse viruses?
Mouse feeder cell
Human PSC
Transplanted cells are rejected when they come from a genetically different donor
Closely matched genetic background increases the probability of a successful transplantation
More cell lines from diverse genetic groups are needed
"No matter how we look at it, the federally approved cell lines are inadequate,we can do a lot of work with them, but we can't move into clinical trials or offer therapies with them.”
J. Gearhart, Johns Hopkins Medical Institute, Panel discussing the clinical use of
PSC/ES cells.
3. Little genetic diversity with existing cell lines
Proprietary issues
Reduced scientific collaboration slows progress
Less ethical oversight
- full disclosure in academia
"the absence of federal funding would mean a reduced role for federal oversight
of the ethics of human embryonic stem cell research.”
Ruth Faden, Ph.D., M.P.H.
Executive Director of the Phoebe R. Berman Bioethics Institute at Johns Hopkins. Panel discussing the clinical use of PSC/ES cells.
4. Pitfalls of relying corporate development
Grow replacementcells
in vitroDerive
Patient-specificcell line
Transplantcells
therapeuticcloning
Somatic cellNuclear transfer
5. Patient specific stem cells:Somatic cell nuclear transfer/Therapeutic cloning
No rejection of transplanted material
Donated surpluseggs from IVF clinics
reproductivecloning
Donated surpluseggs from IVF clinics
Somatic cellNuclear transfer
Transferto uterus
Somatic cell nuclear transferReproductive cloning
reproductivecloning
X
X
All scientists I’ve spoken withthink reproductive cloning is
immoral and should be illegal.
Donated surpluseggs from IVF clinics
Somatic cellNuclear transfer
Transferto uterus
Somatic cell nuclear transferReproductive cloning