User:AriannaB

A potential treatment of PD lies in stem cells and cellular grafts. These cell transplantations could be proliferated in the PD affected brain itself. Stem cells and cell grafts have the ability to differentiate into dopamine-producing cell bodies. The replacement of dopaminergic cells would effectively reverse the disease process to restore normal motor movement. Neural stem cells may be found in an area of the brain called the rostral migratory stream and subventricular zone. The stem cells found in these regions of the brain appear to be particularly sensitive to decreased levels of dopamine. The rostral migratory stream and subventricular zone could provide researchers and physicians with an unlimited supply of dopamine-sensitive stem cells.

Animal model studies
Embryonic precursor cells can proliferate and differentiate successfully within the midbrain of PD rat models to release dopamine, ultimately improving motor functions. Stem cells from the rostral migratory stream and subventricular zone responded in rat models with a rise in dopaminergic cell differentiation. Embryonic stem cell transplantations into mouse models of PD revealed improved motor functions in comparison to control groups. The use of embryonic cells showed an increase in dopaminergic cell survival after transplantation in rat PD models, over adult and fetal sources. PD model rats that underwent treatment with adult stromal cells revealed improvements in motor movement. This restoration of movement suggests that stromal cell transplantation may be a viable technique to treat human PD patients.

The possible inclusion of inappropriate cells in neural stem cell grafts to the midbrain regions is a concerning complication after transplantation. High doses of neurotrophic factor (NTF) are required for the cell grafts to survive the trauma of transplantation. These high doses of NTF have lead to tumor formations in rat models of Parkinson’s. Uncontrolled growth of undifferentiated cells has also been reported to result in teratoma formations in the striatum after stem cell transplantation.

Stem cell treatment in humans
The pathology of Parkinson’s disease may present an environment too hostile for the implanted stem cells and cell grafts to survive for a useful amount of time. However, in autopsies of PD patients who underwent transplantation, a slow rate of disease pathology in grafted stem cells was reported. In addition, a majority of the grafted cells appeared completely unaffected and otherwise healthy.

''The first prospective randomised double-blind sham-placebo controlled trial of dopamine-producing cell transplants failed to show an improvement in quality of life although some significant clinical improvements were seen in patients below the age of 60. A significant problem was the excess release of dopamine by the transplanted tissue, leading to dystonias. Research in African green monkeys suggests that the use of stem cells might in future provide a similar benefit without inducing dystonias .''

Location of stem cell transplantation
In early animal models, fetal cell grafts were transplanted in to the substantia nigra. The transplanted cells failed to project axons to the striatum. Without the restoration of the pathway from the substantia nigra to the striatum, there were no improvements in motor function. In animal models of PD, human fetal cell grafts to the striatum rather than the substantia nigra resulted in a decrease of symptoms. However, not all symptoms were fully remedied in the animal models, and some motor dysfunctions remained as poor as before the graft. The use of neural stem cells altered to over-express an aggregate factor, L1, showed remarkable improvements in cell vitality and motor function when transplanted into the striatum of animal PD models.

Astrocyte differentiation of stem cells
Without the action of the astrocytes and the presence of NTF, brain cells would not survive. It may be possible to differentiate stem cells into astrocytes in the striatum and substantia nigra to protect dopaminergic cells from death induced by the pathology of PD. Past drug administration of NTF in humans appeared to protect the dopamine cells and nerve fibers during the phase I testing. However, the study had to be halted during the phase II test because the treatment appeared to have no effect, or possibly even a detrimental outcome for some of the PD patients in the experiment.

Cited References
1.	Kim J, Auerbach J, Rodriquez-Gomez J, Velasco I. 2002. Dopamine Neurons Derived from Embryonic Stem Cells Function in an Animal Model of Parkinson’s Disease. Nature 418:50-56.

2.	Arias-Carrion, O, Yuan T. 2009. Autologous Neural Stem Cell Transplantation: A New Treatment Option for Parkinson's Disease? Medical Hypotheses 73(5):757-9.

3.	Cui Y, Hargus G, Xu J, Schmid J. 2009. Embryonic Stem Cell-Derived L1 Overexpressing Neural Aggregates Enhance Recovery in Parkinsonian Mice. Brain 2010 133(1):189-204.

4.	Bahat-Stroomza M, Barhum Y, Levy, Y, Karpov O. 2009. Induction of Adult Human Bone Marrow Mesenchymal Stromal Cells into Functional Astrocyte-Like Cells: Potential for Restorative Treatment in Parkinson’s Disease. Journal of Molecular Neuroscience 39:199-210.

5.	Wijeyekoon R, Barker R. 2009. Cell Replacement Therapy for Parkinson’s Disease. Biochimica et Biophysica Acta (ABBA)—Molecular Basis of Disease. 1792(7):688-702.

6.	Lindvall O, Kokaia Z. 2009. Prospects of stem cell therapy for replacing dopamine neurons in Parkinson's disease. Trends in Pharmacological Science. 30(5):260-267.

7.     Freed CR, Greene PE, Breeze RE, et al. (March 2001). "Transplantation of embryonic dopamine neurons for severe Parkinson's disease". The New England Journal of Medicine 344 (10): 710–9.

8.     Redmond DE (October 2002). "Cellular replacement therapy for Parkinson's disease--where we are today?". The Neuroscientist 8 (5): 457–88.

9.     Redmond E et al (2007). "Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells". Proceedings of the National Academy of Sciences 104 (29): 12175.

10.	Office of Communications and Public Liaison. 2010 [cited 2010 Feb 13]. Parkinson's Disease: Hope through Research. [Internet]. Bethesda, MD: National Institute of Neurological Disorders and Stroke. Available from: http://www.ninds.nih.gov/disorders/parkinsons_disease/detail_parkinsons_disease.htm.