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Jim Wells, Ph.D

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Somatic cell nuclear transfer/Therapeutic cloning. No rejection of transplanted material ... think reproductive cloning is. immoral and should be illegal. ... – PowerPoint PPT presentation

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Title: Jim Wells, Ph.D


1
Stem cell potential
  • Jim Wells, Ph.D
  • Assistant Professor
  • Division of Developmental Biology
  • Childrens Hospital
  • Research Foundation of Cincinnati
  • James.wells_at_cchmc.org
  • 513-636-8767

2
Google search for human stem cell ethics
1
Google Hits (x 1,000,000)
2700 increase
0.5
August 2005
2004
2002
2003
3
(10 type 1)
4
Stem cells
Pluripotent embryonic stem cells PSCs
Adult stem cells
Also cord blood stem cells
5
Goal of all stem cell research
stem cell
PSC/ES cells
in vitro
Adult stem cells
Make Therapeutic Cells in vitro (in a petri dish)
Therapeutic cell
Cure disease
6
Source of pluripotent/embryonic stem cells
20 cells
0.1mm 4/1000th inch
Human embryo 4 days after in vitro fertilization
Eye of a needle
7
Making pluripotent Stem Cell lines
Donated surplus eggs from IVF clinics
Cell Line
Cells will grow Indefinitely in a petri
dish Make billions of copies Limitless supply
of Potential therapeutic cells
Other options
Keep Frozen
Discard as medical waste
It is esimated that 400,000 surplus eggs are
stored/frozen in the US
8
Pluripotent Stem Cell lines
Cell line 1
Wisconsin
Cell line 2
Göteborg
Cell line 3
Haifa
9
Examples of what PSCs can become
(Crohnes disease)
(Alzheimers Multiple Sclerosis)
Gut cells
(Oteoporosis)
Brain neurons
Bone cells
Spinal cord neurons
(Muscular Dystrophy)
Muscle cells
(Paralysis)
Potential limitless supply of any diseased cell
Skin cells
Heart cells
(Burns)
(Cardiovascular disease)
Blood cells
b-cells
(Diabetes)
(Anemia, Cancer)
10
Examples of Adult stem cells
Skin stem cells
?
Blood stem cells
X
No adult stem cell for b-cells in vivo
50,000,000,000,000 total cells
Muscle stem cells
11
Comparison of stem cells
  • First isolated in November, 1998
  • Pluripotent - can become all cell
  • types of the body
  • Can multiply indefinitely in vitro
  • Un-tested therapeutically

Human PSCs
  • First identified 4 decades ago
  • Multipotent - can become some
  • cell types of the body
  • Limited replication in vitro
  • Some therapeutics available

Human adult SCs
12
Future stem cell therapeutics
Human PSCs
  • Diabetes
  • Alzheimers
  • Stroke
  • Cardiovascular disease
  • Autoimmune disease
  • Parkinsons
  • Cancer
  • Burns
  • Spinal chord injury
  • Birth defects

?
?
Human adult SCs
13
Future stem cell therapeutics
  • Alzheimers
  • Cardiovascular disease
  • Cancer
  • Burns
  • Spinal chord injury

?
Human adult SCs
14
Future stem cell therapeutics
Human PSCs
  • Diabetes
  • Stroke
  • Autoimmune disease
  • Parkinsons
  • Birth defects

?
15
Future stem cell potential We dont yet know
which type of stem cell will ultimately cure
these different diseases
16
Approved pluripotent Stem Cell lines
Cell line 1
Wisconsin
Cell line 2
Göteborg
Cell line 3
Haifa
There are between 11 and 20 approved lines
available at the stem cell registry at the
National Institutes of Health. Developed before
August 2001
17
Current stem cell lines have limited therapeutic
potential because
  • Significant differences exist between cell lines
  • Grown with mouse cells as feeders
  • Little genetic diversity
  • Corporate funding/proprietary issues
  • Excludes use of patient-specific cell lines

18
  • Significant differences between cell lines
  • Physically different
  • Genetically different/chromosomal abnormalities
  • Multiply differently
  • Differences in their ability to become
    therapeutic cell types?

19
Are these differences important?
Different lines may have different therapeutic
potential, or none at all
?
Wisconsin
b-cells
?
NOTHING
Göteborg
?
Haifa
nerves
Hundreds of different cell types in the body
affected by disease
20
  • 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
Human PSC
Mouse viruses?
Mouse feeder cell
21
  • Little genetic diversity with existing cell lines

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.
22
  • Pitfalls of relying corporate development

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.
23
5. Patient specific stem cells Somatic cell
nuclear transfer/Therapeutic cloning
Donated surplus eggs from IVF clinics
Grow replacement cells in vitro
Derive Patient-specific cell line
Transplant cells
therapeutic cloning
No rejection of transplanted material
Somatic cell Nuclear transfer
24
Somatic cell nuclear transfer Reproductive cloning
Donated surplus eggs from IVF clinics
Transfer to uterus
reproductive cloning
Somatic cell Nuclear transfer
25
Somatic cell nuclear transfer Reproductive cloning
X
Donated surplus eggs from IVF clinics
X
Transfer to uterus
reproductive cloning
All scientists Ive spoken with think
reproductive cloning is immoral and should be
illegal.
Somatic cell Nuclear transfer
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