PARKINSON DISEASE- SPECIFIC INDUCED PLURIPOTENT STEM

CELLS

By: Sara Camille Díaz Méndez

Rise Program

What is Parkinson’s?• definition

• How many people does it affect?

• cause

• What does Parkinson involve?

Role of Neurons in Parkinson’s

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

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?

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

Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease

• 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)

Keywords

embryonic stem cells reprogramming cell transplantation Tyrosine hydroxylase (TH)

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)

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)

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

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

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.

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.

Cited Literature:

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