PHENOTYPIC DEVELOPMENT OF THE HUMAN EMBRYONIC STRIATAL PRIMORDIUM - ASTUDY OF CULTURED AND GRAFTED NEURONS FROM THE LATERAL AND MEDIAL GANGLIONIC EMINENCES

Basic parameters which are crucial for the survival of human embryonic striatal grafts need to be investigated before initiating clinical tr ials in Huntington's disease. In order to define the dissection of hum an striatal donor tissue which gives rise to the largest amount of str iatal neurons after intrastriatal transplantation, we studied the late ral and medial ganglionic eminences of embryonic striatal primordia ob tained from human embryos sized 17-30 mm in crown-to-rump length (corr esponding to Carnegie stages 18-23). Anatomical landmarks that demarca ted the lateral and medial ganglionic eminences from each other were p resent only in embryos with 20 mm crown-to-rump length or larger. In m onolayer cultures, the lateral ganglionic eminence gave rise to a six- fold higher yield of dopamine- and cyclic AMP-regulated phosphoprotein 32-immunoreactive striatal neurons as compared to the medial ganglion ic eminence. We also xenografted the lateral and medial ganglionic emi nences from five embryos sized 21-30 mm in crown-to-rump length to the ibotenate lesioned striatum of immunosuppressed rats. The grafts were evaluated with respect to general morphology, survival and integratio n using (immuno-) histochemical stains for acetylcholinesterase/Cresyl Violet, nicotinamide adenine dinucleotide phosphate-diaphorase, dopam ine- and cyclic AMP-regulated phosphoprotein-32, tyrosine hydroxylase and calbindin-D28KD. As assessed 9-25 weeks after implantation, 13 out of 16 and 8 out of 13 grafts, in the groups grafted with the medial a nd lateral ganglionic eminences, respectively, had survived. Previous studies with rat donor tissue have indicated that the functional effic acy of striatal grafts is related to the development of striatal-speci fic P-zone regions and that these are enriched in transplants derived from the lateral as opposed to the medial ganglionic eminence. Also in the human striatal xenografts of the present study, P-zones appeared more abundant when the donor tissue was derived from the lateral gangl ionic eminence. However, the proportion of graft tissue that expressed P-zone properties was always very low (at most 30%) and never approac hed the 80-90% previously observed in transplants of rat lateral gangl ionic eminence. We conclude that the relative yield of striatal neuron s in grafts of the human embryonic striatal primordium has to be impro ved before neural transplantation should be applied in patients with H untington's disease. (C) 1996 IBRO. Published by Elsevier Science Ltd.