This document discusses the potential use of induced pluripotent stem cells (iPSCs) derived from fibroblasts for treating Parkinson's disease. It summarizes that iPSCs can be generated from adult fibroblasts through retroviral transduction of specific transcription factors. One study discussed found that when neurons derived from reprogrammed mouse fibroblasts were transplanted into a rat model of Parkinson's, they functionally integrated into the brain and improved motor symptoms. The document concludes that while iPSC-derived cells show promise for treating Parkinson's, more research is still needed to address safety issues before applying this technique to humans.

1. PARKINSON DISEASE- SPECIFIC
INDUCED PLURIPOTENT STEM
CELLS
By: Sara Camille Díaz Méndez
Rise Program

2. What is Parkinson’s?
• definition
• How many people does it affect?
• cause
• What does Parkinson involve?

3. Role of Neurons in Parkinson’s

4. Parkinson’s Disease
 neurological disorders (Wicks 2008)
- slowness (bradykinesia)
- stiffness
- tremor
 mean age onset: 60’s-70’s (Wicks 2008)
- 10% of patients before 40
- known as “young onset” PD (YOPD)
 non-motor symptoms (Wicks 2008)
- apathy, hallucinations
- depression, anxiety
- constipation, bladder urgency

5. The use of stem cells for Parkinson
treatment
• Stem cells are a renewable source of tissue that can be coaxed
to become different cell types of the body. (Fox 2009)
• How are they created?

6. Neurons derived from reprogrammed fibroblasts functionally integrate
into the fetal brain and improve symptoms of rats with Parkinson's
disease
• Embryonic stem (ES) cells
• What is the problem?
• possible solution
• article #1

7. Neurons derived from reprogrammed fibroblasts functionally integrate into the
fetal brain and improve symptoms of rats with Parkinson's disease
Keywords
 embryonic stem cells
 reprogramming
 cell transplantation
 Tyrosine hydroxylase (TH)
• somatic cell nuclear transfer - embryonic stem cells (SCNT-ES)
• therapeutic potential
• “In vitro reprogramming of mouse fibroblasts into pluripotent stem cells (iPS)
was achieved through retroviral transduction of the four transcription factors
(Oct4, Sox2, c-Myc and Klf4) and selection for reactivation of the ES cell marker
gene Fbx15.” (Werning et all 2008)

8. Neurons derived from reprogrammed fibroblasts functionally integrate into
the fetal brain and improve symptoms of rats with Parkinson's disease
• migratory capacity
• “Our data shows that iPS cell-derived neurons synaptically integrate
after transplantation into the fetal mouse brain and function after
transplantation into the adult brain in a rat model of Parkinson’s
disease.” (Werning et all 2008)

9. Results
• successful transplantation and immigration of iPs into neurons
• The highest densities of transplanted cells were found in septum,
striatum, hypothalamus and midbrain. (Werning et all 2008)

10. Functional Recovery of Parkinsonian Rats After Transplantation
of iPS Cell-Derived Midbrain Dopamine Neurons.
• “Electrophysiological recordings from brain slices prepared
from transplanted animals were used to examine functional
neuronal properties in the engrafted cells.” (Werning et all 2008)
• reprogrammed fibroblasts were differentiated into dopamine
neurons
• fourth week- no TH-positive elements present in the Substantia
Nigra

11. Functional Recovery of Parkinsonian Rats After Transplantation
of iPS Cell-Derived Midbrain Dopamine Neurons.
• fourth week: Large number of TH-positive cells were
found in the striatum
• TH- immunoreactive fibers were present
• four of five transplanted animals showed a marked
recovery

12. Conclusion
• Findings demonstrate that direct reprogramming is
functionally equivalent to “therapeutic cloning” by nuclear
transfer but future investigations need to be done in order
eliminated complications before this technique can be
safely applied in humans.

13. What is the future for stem cell research?
• Long-term studies are awaited to determine whether
the transplanted stem cells will eventually degenerate
much like the natural dopamine cells affected by the
ongoing Parkinson’s process.

14. Cited Literature:
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• 2. Hochedlinger K, Jaenisch R. Nuclear transplantation, embryonic stem cells, and the potential for cell therapy. N Engl J Med.
2003;349:275–286.
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• 4. Werning IL. Medicine: Politic stem cells. Nature. 2006;439:145–147.
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cell and gene therapy. Cell. 2002;109:17–27.
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2001;292:740–743.
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Nat Biotechnol. 2008;21:1200–1207.
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2006;126:663–676.
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Wernig M, et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature. 2007;448:318–324.
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