Intrastriatal and intranigral grafting of hNT neurons in the 6-OHDA rat model of Parkinson's disease.
The clinical findings on neural transplantation for Parkinson's disease (PD) reported thus far are promising but many issues must be addressed before neural transplantation can be considered a routine therapeutic option for PD. The future of neural transplantation for the treatment of neurological disorders may rest in the discovery of a suitable alternative cell type for fetal tissue. One such alternative may be neurons derived from a human teratocarcinoma (hNT). hNT neurons have been shown to survive and integrate within the host brain following transplantation and provide functional recovery in animal models of stroke and Huntington's disease. In this study, we describe the transplantation of hNT neurons in the substantia nigra (SN) and striatum of the rat model for PD. Twenty-seven rats were grafted with one of three hNT neuronal products; hNT neurons, hNT-DA neurons, or lithium chloride (LiCl) pretreated hNT-DA neurons. Robust hNT grafts could be seen with anti-neural cell adhesion molecule and anti-neuron-specific enolase immunostaining. Immunostaining for tyrosine hydroxylase (TH) expression revealed no TH-immunoreactive (THir) neurons in any animals with hNT neuronal grafts. THir cells were observed in 43% of animals with hNT-DA neuronal grafts and all animals with LiCl pretreated hNT-DA neuronal grafts (100%). The number of THir neurons in these animals was low and not sufficient to produce significant functional recovery. In summary, this study has demonstrated that hNT neurons survive transplantation and express TH in the striatum and SN. Although hNT neurons are promising as an alternative to fetal tissue and may have potential clinical applications in the future, further improvements in enhancing TH expression are needed.
Baker
K A
KA
Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada.
Hong
M
M
Sadi
D
D
Mendez
I
I
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D002452:Cell Count; D002460:Cell Line; D003342:Corpus Striatum / Q000201:enzymology / Q000473:pathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006085:Graft Survival; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000637:transplantation*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013378:Substantia Nigra / Q000201:enzymology / Q000473:pathology*; D018243:Teratocarcinoma; D014183:Transplantation, Heterologous; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D018021:Lithium Chloride; D004298:Dopamine