ONTOGENY OF EMBRYONIC PORCINE VENTRAL MESENCEPHALON IN THE PERSPECTIVE OF ITS POTENTIAL USE AS A XENOGRAFT IN PARKINSONS-DISEASE

Human fetal neural dopaminergic tissue can be transplanted and can ame liorate neurological deficiencies in patients with Parkinson's disease (PD). Donor tissue from other species has been used experimentally fo r several years in animal experiments and is now being considered an a ttractive alternative, particularly from a donor species that breeds i n large Litters, e.g., the pig. We have studied the early ontogenetic development of the mesencephalic dopaminergic system in the pig, utili sing an anti-tyrosine hydroxylase (TH) immunocytochemical technique, a nd demonstrated the earliest appearance of its cell bodies at embryoni c day 20 (E20). We compared the porcine data with those of human fetal development, as revealed by the same technique. Embryonic dopaminergi c cell groups resembling the A8, A9, and A10 of the rat are present in the pig and differentiate into the homologous cell groups of human, a lthough interesting quantitative differences are apparent. In the pig, prolonged presence of immature characteristics of TK-immunoreactive ( TH-i.r.) cell bodies was observed, notwithstanding the early outgrowth of TH-i.r. axons into the ganglionic eminence. In the human, on the o ther hand, cell divisions and maturation of dendrites have progressed to a further degree than in the pig, before such distinct outgrowth of axons takes place. In pig embryos of 28 days, cells in the ventral me sencephalon had differentiated into TH containing neurons, which indic ates their potential to synthesize dopamine. In spite of their differe ntiation, these cells still showed immature morphological features (ro unded cell bodies with undifferentiated, short processes). Dopamine sy nthesis by these cells was demonstrated in previous studies by the hig h performance liquid chromatographic technique (HogenEsch et al. [1993 ] Can. J. Neurol. Sci. 20(suppl. 4):P.S. 235). In a separate paper, we have described that these porcine 28-day dopaminergic cells retain th eir potential for development and outgrowth in culture (van Roon et al . [1995] Res. Neurol. Neurosci. 7:199-205). We conclude that the ventr al mesencephalon in pig embryos of 28 days is a potential source of do paminergic neurons to be used as a xenograft in PD. (C) 1997 Wiley-Lis s, Inc.