Ventriculoscopically harvested adult neural stem cells from the subventricular zone: a possible source for dopaminergic cells for neurotransplantation in Parkinson's Disease?

Parkinson's Disease (PD) is a common neurodegenerative dissorder affecting
approximately 1% of the population over 60 years of age. In PD patients a
dopamine (DA) shortage develops, caused by the idiopathic progressive
degeneration of DA-producing neurons. This causes the cardinal symptoms:
bradykinesia, rigidity and tremor. Current treatment consists mainly of
pharmacological subsitution of levodopa. Long-term usage of this dopamine
causes serious adverse effects e.g. dyskinesia, the on/off phenomenon. Using
neuromodulative operations can alleviate these levodopa induced adverse effects
in selected patients. The shortcomings of current treatment strategies led to a
search for alternatives. In recent years cell transplantation therapy has
gained attention as a possible new treatment internationally. In Groningen
there has been 15 years of experience in investigations for cell
transplantation therapy for PD. The purpose of cell transplantation is to
implant DA-producing neurons to relieve the existing DA-shortage. Different
tissue sources for neural grafting have been investigated (e.g. human fetal and
pig fetal neurons). All tissue sources investigated up to date have practical
(availability, immunologic rejection) and ethical problems. Stem cells are a
promising new tissue source. Stem cells are able to proliferate and
differentiate. There are different types of stem cells: toti-, pluri-, and
multipotent with a varying potential to differentiate into adult cells.
Totipotent stem cells have the largest potential, multipotent stem cells are
only able to differntiate into the cell lineage of the organ from which they
originated. Together with the Department of Medical Physiology experience was
gained in the treatment of rat and mouse derived stem cells. It has been shown,
that multipotent stem cells are present the subventricular zone that can
differentiate into the different cell types of the adult central nervous
system. Furthermore, it has been shown, that these cells are relatively easy to
obtain and can be differentiated into DA-producing neurons. These cells form an
interesting source for neural grafting, which lack the practical
(immunological) and ethical concerns of previously investigated tissue sources.

Development of a cell transplantation therapy for PD through autologous stem
cells.

Patients who need ventriculoscopy will be asked to donate the small piece of
tissue that is detached from the ventricular wall during introduction of the
ventriculoscope. Subsequently this tissue will be processed in vitro to try and
isolate DA producing neurons.

The risks associated with participation are neglectable. It has been shown that
it is safely possible to harvest the tissue sample we are interested in (1).
The procedure will be performed by an experienced ventriculoscopist. The
procedure will only take a few minutes more. During this period the patient is
anaesthetized. In addition to routine laboratory blood investigations patients
will be tested for inflammatory parameters during work-up. Obtained tissue will
be processed outside the patients body.





1 Westerlund U, Svensson M, Moe MC, et al Endoscopically harvested stem cells:
a putative method in future autotransplantation. Neurosurg 2005 Oct;
57(4):779-84