TY - JOUR
T1 - Transplantation of human striatal tissue into a rodent model of huntington's disease
T2 - Phenotypic expression of transplanted neurons and host-to-graft innervation
AU - Pundt, Lisa L.
AU - Kondoh, Takeshi
AU - Conrad, John A.
AU - Low, Walter C
N1 - Funding Information:
The authors would like to thank Joan Aanderud and Linda King for expert clerical and administrative assistance. This work was supported in part by NIH Grants R24-HD-30511 and RO1-NS-24464.
PY - 1996
Y1 - 1996
N2 - The present study was undertaken to investigate the phenotypic expression and integration of human striatal neurons transplanted into an animal model of Huntington's disease. Sprague-Dawley rats were anesthetized and subjected to quinolinic acid lesions of the left striatum. Three human fetal cadavers were utilized for transplantation in this study (7,8, and 10 weeks in gestation). The striatal primordia was dissected from each fetus and subsequently dissociated into cell suspensions. Following the initial lesion surgeries (3-4 months), the rats were reanesthetized and transplanted with human striatal cells (400,000 cells per rat). The animals were processed for histochemical analysis 9-17 weeks posttransplantation. Histochemistry was performed utilizing thionin (Nissl staining), acetylcholinesterase, NADPH-diaphorase, and antibodies against tyrosine hydroxylase and glial fibrillary acidic protein. Examination of stained brain sections demonstrate that human striatal transplants grow to fill a substantial portion of the remaining striatum, and contain clusters of immature and mature cells. Acetylcholinesterase activity is present in the transplant neuropil, varying in intensity, and distributed in a heterogeneous fashion. In addition, host afferent dopaminergic fibers penetrate into the transplant, and are occasionally found in patches. NADPH-diaphorase histochemistry revealed medium sized aspiny striatal neurons of donor origin in the transplants. The results of this study are similar to those obtained with rodent fetal striatal transplants, and suggest that human striatal tissue is capable of surviving, expressing normal striatal cell phenotypes, and receiving host dopaminergic innervation.
AB - The present study was undertaken to investigate the phenotypic expression and integration of human striatal neurons transplanted into an animal model of Huntington's disease. Sprague-Dawley rats were anesthetized and subjected to quinolinic acid lesions of the left striatum. Three human fetal cadavers were utilized for transplantation in this study (7,8, and 10 weeks in gestation). The striatal primordia was dissected from each fetus and subsequently dissociated into cell suspensions. Following the initial lesion surgeries (3-4 months), the rats were reanesthetized and transplanted with human striatal cells (400,000 cells per rat). The animals were processed for histochemical analysis 9-17 weeks posttransplantation. Histochemistry was performed utilizing thionin (Nissl staining), acetylcholinesterase, NADPH-diaphorase, and antibodies against tyrosine hydroxylase and glial fibrillary acidic protein. Examination of stained brain sections demonstrate that human striatal transplants grow to fill a substantial portion of the remaining striatum, and contain clusters of immature and mature cells. Acetylcholinesterase activity is present in the transplant neuropil, varying in intensity, and distributed in a heterogeneous fashion. In addition, host afferent dopaminergic fibers penetrate into the transplant, and are occasionally found in patches. NADPH-diaphorase histochemistry revealed medium sized aspiny striatal neurons of donor origin in the transplants. The results of this study are similar to those obtained with rodent fetal striatal transplants, and suggest that human striatal tissue is capable of surviving, expressing normal striatal cell phenotypes, and receiving host dopaminergic innervation.
KW - Acetylcholinesterase
KW - NADPH
KW - Quinolinic acid
KW - Tyrosine hydroxylase
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U2 - 10.1016/0361-9230(95)02029-2
DO - 10.1016/0361-9230(95)02029-2
M3 - Article
C2 - 8846104
AN - SCOPUS:0030029924
SN - 0361-9230
VL - 39
SP - 23
EP - 32
JO - Brain Research Bulletin
JF - Brain Research Bulletin
IS - 1
ER -