Transplantation of expanded neural precursor cells from the developing pig ventral mesencephalon in a rat model of Parkinson's disease

Neural precursor cell populations can be expanded in vitro under the influence of growth factors, and may be of use to replace cells lost to neurodegenerative conditions such as the dopaminergic neurons in Parkinson's disease (PD). We explore here whether expanding neural precursor cells from the region in which nigral dopaminergic neurones emerge in normal development renders them more likely to differentiate into TH-positive neurones when transplanted in a rat model of PD. Embryonic neural precursor cells (ENPs) were isolated from the developing pig ventral mesencephalon (VM) at two different gestational ages and were implanted into the striatum or the substantia nigra of cyclosporin A-immunosuppressed, 6-hydroxydopamine-lesioned rats, which were sacrificed 9 or 18 weeks later. The properties of ENPs varied according to the gestational age of the donor: ENPs that expanded robustly and survived transplantation could be derived from E22 VM, but not from E27 VM. ENPs developed into neurones that displayed diffuse fibre projections, including those appropriate for the implantation site. However, behaviourally significant numbers of TH-positive neurones were not seen. A rejection response was apparent in most animals by 18 weeks. These data show that donor age is an important variable when deriving ENPs for transplantation. Furthermore, derivation of ENPs from the VM at the time of normal dopaminergic neurogenesis is inadequate to ensure functional dopaminergic grafts on transplantation.