Gene therapy in hemiparkinsonian rhesus monkeys: long-term survival and behavioral recovery by transplantation of autologous human tyrosine hydroxylase-expressing neural stem cells.
OBJECTIVE
Neural stem cells (NSC) derived from bone marrow stromal cells (BMSC) (BMSC-D-NSC) are remarkably versatile in response to environmental signals, which render them useful in the search for neurodegenerative disease treatments.


METHODS
We isolated NSC from rhesus monkey bone marrow (BM), transfected them with the human tyrosine hydroxylase (hTH) gene, and transplanted them into 1-methyl-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned hemiparkinsonian rhesus monkeys to determine changes in neural transmitter production and alterations in behavior.


RESULTS
hTH-expressing cells produced monoamine agents in vitro, such as noradrenalin and dopamine. After cell transplantation in the caudate nucleus and substantia nigra of the experimental monkeys, their disease symptoms and dysfunctional glucose metabolism and dopamine transport were ameliorated.


CONCLUSIONS
hTH-expressing BMSC-D-NSC survived in transplantation sites and assumed normal dopaminergic neuronal properties, playing an instrumental role in functional restoration.
Xu
Qiang
Q
Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China 510282.
Jiang
Xiaodan
X
Ke
Yiquan
Y
Zhang
Shizhong
S
Xu
Ruxiang
R
Zeng
Yanjun
Y
D000818:Animals; D001522:Behavior, Animal; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D049109:Cell Proliferation; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D020267:MPTP Poisoning; D008253:Macaca mulatta; D008297:Male; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D011180:Postmortem Changes; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D016019:Survival Analysis; D013997:Time Factors; D014182:Transplantation, Autologous; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism / Q000627:therapeutic use*
C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase