Human fetal neural dopaminergic tissue can be transplanted and can ameliorate neurological deficiencies in patients with Parkinson's disease (PD). Donor tissue from other species has been used experimentally for several years in animal experiments and is now being considered an attractive alternative, particularly from a donor species that breeds in large litters, e.g., the pig. We have studied the early ontogenetic development of the mesencephalic dopaminergic system in the pig, utilising an anti-tyrosine hydroxylase (TH) immunocytochemical technique, and demonstrated the earliest appearance of its cell bodies at embryonic day 20 (E20). We compared the porcine data with those of human fetal development, as revealed by the same technique. Embryonic dopaminergic 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, although interesting quantitative differences are apparent. In the pig, prolonged presence of immature characteristics of TH-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 other 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 mesencephalon had differentiated into TH containing neurons, which indicates their potential to synthesize dopamine. In spite of their differentiation, these cells still showed immature morphological features (rounded cell bodies with undifferentiated, short processes). Dopamine synthesis by these cells was demonstrated in previous studies by the high 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 their potential for development and outgrowth in culture (van Roon et al. [1995] Res. Neurol. Neurosci. 7:199-205). We conclude that the ventral mesencephalon in pig embryos of 28 days is a potential source of dopaminergic neurons to be used as a xenograft in PD.

Human fetal ventral mesencephalon tissue has been used as dopaminergic striatal implants in Parkinsonian patients, so far with variable effects. Fetuses from animals that breed in large litters, e.g., pigs, have been considered as alternative donors of dopaminergic tissue. The optimal gestational age of the porcine fetal donors has not been studied systematically. We collected ventral mesencephalic (VM) tissue from fetal pigs, embryonal ages E21, E28, E42, and E70, and examined the viability of the fetal VM cells after dissociation, the expression of tyrosine hydroxylase (TH) in culture, the presence of catecholamines, and the cellular survival and outgrowth up to 10 months after intrastriatal implantation in rats. The highest viability was found in suspensions prepared from E28 fetuses. The highest number of TH-positive cells was found in cell cultures prepared from E28 VM tissue. Explants with a gestational age of 28 and 42 days contained the largest amount of dopamine. Only E28-derived grafts showed TH-cell survival after implantation in rat striatum. Our results show that a gestational age of 28 days must be considered to be the optimal age for dopaminergic tissue derived from pig fetuses for therapeutic use as intrastriatal grafts in Parkinsonian patients.

There is increasing interest in the use of human fetal dopaminergic tissue as a source of striatal transplant in parkinsonian patients. This tissue is acquired by elective abortions. The possibilities of the use of this tissue were studied by macro-scopical examination, cell-culturing followed by immunohistochemical staining and by high performance liquid chromatography. It turned out that 50% of the curettages obtained by suction abortion were too fragmented to reliably recognize the dopamine-containing area (ventral mesencephalon). Furthermore, dissection of the brainstem immediately after the abortion procedure seemed to be of utmost importance.

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