ORGANIZATION AND HISTOCHEMICAL PHENOTYPE OF HUMAN FETAL CEREBELLAR CELLS FOLLOWING TRANSPLANTATION INTO THE CEREBELLUM OF NUDE-MICE

Previous rodent studies have demonstrated the capacity of cerebellar t ransplants to organize into trilaminar cell layers typically observed in the normal cerebellum. In Purkinje Cell (PC)-deficient animals, PCs will migrate into the host and form synaptic connections, Recently, f etal cerebellar grafts transplanted into the Purkinje cell degeneratio n (pcd) mutant mouse were shown to result in an improvement of motor b ehaviors. These studies indicate the potential therapeutic use of neur al transplantation in patients with cerebellar degeneration, In the pr esent study, human fetal cerebellar tissue (8.5 wk postconception) was dissociated and transplanted into the normal cerebellum of nude mice, Six months following transplantation, histological analysis revealed donor cells in recipient mice. Immunostaining for the 28 kDa calcium-b inding protein (calbindin) revealed the presence of donor PCs that wer e organized in discrete cellular layers within the transplant neuropil , In most cases the dendritic processes were oriented in a planar fash ion perpendicular to the transplant cell layer, Human neurofilament im munostaining revealed bundles of donor fibers within the core of the t ransplant and/or at the periphery, These bundles were found to be calb indin positive (PC fibers), Three animals provided evidence of donor P C axon growth ventrally into host white matter, and in one case, this ventral migration reached the deep cerebellar nuclei, Most notable was the development of a pronounced folia-like organization by the implan ted cell suspensions, Glial processes within the grafts were aligned p erpendicular to the long axis of the transplant folia, These results d emonstrate the capacity of human fetal cerebellar cell suspension to r eorganize into cell layers typical of the normal cerebellum following transplantation into the rodent cerebellum, and develop an organotypic folia-like organization. (C) 1997 Elsevier Science Inc.