Human ventral mesencephalic xenografts to the catecholamine-depleted striata of athymic rats: ultrastructure and immunocytochemistry.
On the basis of animal studies, grafts of fetal human dopaminergic cells have been suggested as a therapy for Parkinson's disease. The purpose of this study was to characterize the ultrastructure and immunocytochemistry of human ventral mesencephalic xenografts placed into the catecholamine-depleted striata of athymic "nude" rats. Human fetal tissue was obtained from tissue fragments derived from elective abortions during the first trimester of pregnancy. Small pieces of the basal mesencephalon were grafted into the catecholamine-depleted striata of four athymic nude rats. The rats were allowed to survive from 3 to 6 months after grafting; following fixation, the striatal tissue containing the grafts was labeled with antibodies against tyrosine hydroxylase and serotonin. Immunocytochemistry revealed tyrosine-hydroxylase-like-immunoreactive (THLI) and serotoninlike-immunoreactive (5HTLI) cell bodies within the human grafts. Both 5HTLI and THLI fibers crossed the graft-host interface and innervated the previously lesioned striatum. Both types of fibers also entered the host cortex from the adjacent human graft. At the ultrastructural level, THLI and 5HTLI fibers and synaptic terminals were observed in the host neuropil. THLI and 5HTLI dendrites and axon terminals were also observed in the neuropil of the grafts themselves. THLI axon terminals are not normally present in the substantia nigra. The results of our study indicate that human xenografts can survive in the neuropil of the host striatum and form morphologically appropriate synapses within the host brain.
Mahalik
T J
TJ
Department of Cellular and Structural Biology, University of Colorado Medical School, Denver 80262.
Strömberg
I
I
Gerhardt
G A
GA
Granholm
A C
AC
Seiger
A
A
Bygdeman
M
M
Olson
L
L
Hoffer
B J
BJ
Finger
T E
TE
D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D005333:Fetus; D006085:Graft Survival; D006801:Humans; D007150:Immunohistochemistry; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D008854:Microscopy, Electron; D051381:Rats; D011922:Rats, Mutant Strains / Q000502:physiology*; D011923:Rats, Nude / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D002395:Catecholamines; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase