[Abstract Title]. - Society for Neuroscience

Abstract: The present study was designed to determine the potential for hUCB stem cells, the
CD133 subset of the hematopoietic mononuclear fraction, to repair, replace, or induce
regeneration of the damaged tissue, loss of dopamine (DA) in the striatum, or the loss of
dopaminergic neuron in adult rats lesioned with the DA neurotoxin, 6-hydroxydopamine, which
model‟s Parkinson‟s disease (PD). Presently, one published study investigated the transplantation
of hUCB cells into an animal model of PD, and showed the lifespan of PD mice were extended
compared to PD mice receiving congenic bone marrow cells or no treatment. The mononuclear
fraction of hUCB cells are well-established and a reliable source cells that are known to be rich
in hematopoietic stem cells, and have been used successfully for over 15 year to treat children
with malignant and non-malignant diseases.
In this study, the CD133 stem cells were first cultured in proliferation media [Stemline
Hematopoietic media (Sigma)] treated with the human recombinant proteins stem cell factor,
thrombooietin, and interleukine-3 for 5 to 10 days in vitro (DIV). The media was either changed
to neural induction media consisting of the Stemline media with never growth factor and all-trans
retinoic acid for 7 to 21 DIV or the Stemline media without the neural induction factors. The
CD133 stem cells formed neurospheres with cells differentiating by 5 DIV as they migrated
away from the aggregate. Therefore, CD133 neural induced and non-induce cells were
transplanted at day 4 in culture, which is before they fully differentiation and are still consider
neural stem cells. A total of 1 X 10 6 cells, were transplanted into the striatum of rats 4 weeks
after receiving 6-OHDA in middle forebrain bundle at two lesion sites. Behavioral testing was
preformed pre-lesion, post-lesion, and post-cell transplant. Rats were sacrificed 2 months after
cell transplants.
Cell culture results showed CD133 cells, cultured in neural induction media, were immunopositive
for all 3 neural lineages, with an average of 45 to 50% of cells labeling positive for DA
and Nurr1 early during the neural induction process (4 to 7 DIV), with 40 to 45% of cells
labeling positive for DA after 7 to 21 DIV, and a decrease in the number of Nurr1 positive cells
after 7 DIV. Several other neuronal markers were also examined in vitro and in vivo. The
behavioral tests have shown behavioral improvements in the 6-OHDA lesioned/CD133
transplanted rats. All of the behavioral tests and the other dependent measures which include DA
cell counts in the striatum and substantia nigra, human specific marker cell counts in several
areas of the brain, the peripheral blood, bone marrow, and spleen will be presented.
Disclosures: M.B. Newman, None; L.P. Kelly, None; A.P. Smith, None; R.A.E. Bakay, None.
Poster
247. Parkinson's Disease Interventions: Animal and Clinical Models
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 247.13/S8
Topic: C.02.d. Therapies