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a Department of Neurology, Agnes Ginges Center for Human Neurogenetics,
b Hadassah Embryonic Stem Cell Research Center, Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, Israel;
c Monash Institute of Reproduction and Development, Monash University, Australia;
d Department of Obstetrics and Gynecology, Hadassah University Hospital, Jerusalem, Israel
Key Words. Parkinson’s disease • Cell therapy • Human ES cells
Correspondence: Benjamin E. Reubinoff, M.D., Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Ein-Kerem, P.O.B. 12,000, Jerusalem, Israel 91120. Telephone: 972-2-6778589; Fax: 972-2-6430982; e-mail: reubinof{at}md2.huji.ac.il
Human embryonic stem cells (hESCs) may potentially serve as a renewable source of cells for transplantation. In Parkinson’s disease, hESC-derived dopaminergic (DA) neurons may replace the degenerated neurons in the brain. Here, we generated highly enriched cultures of neural progenitors from hESCs and grafted the progenitors into the striatum of Parkinsonian rats. The grafts survived for at least 12 weeks, the transplanted cells stopped proliferating, and teratomas were not observed. The grafted cells differentiated in vivo into DA neurons, though at a low prevalence similar to that observed following spontaneous differentiation in vitro. Transplanted rats exhibited a significant partial correction of D-amphetamine and apomorphine-induced rotational behavior, along with a significant improvement in stepping and placing non-pharmacological behavioral tests. While transplantation of uncommitted hESC-derived neural progenitors induced partial behavioral recovery, our data indicate that the host-lesioned striatum could not direct the transplanted neural progenitors to acquire a dopaminergic fate. Hence, induction of their differentiation toward a midbrain fate prior to transplantation is probably required for complete correction of behavioral deficit. Our observations encourage further developments for the potential use of hESCs in the treatment of Parkinson’s disease.
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