High titer retroviral gene transduction to neural progenitor cells for establishment of donor cells for neural transplantation to parkinsonian model rats.
Neural progenitor cells (NPCs) are expected to be useful donor sources for cell transplantation therapy in Parkinson's disease. However, control of the differentiational lineage, especially into dopaminergic neurons, is still difficult. Thus, genetic modification of NPCs to produce l-dopa is potentially useful. The present study prepared high titer retrovirus carrying human tyrosine hydroxylase-1 (HTH-1) gene. HTH-1 gene could be efficiently transduced into NPCs obtained from the E12.5 rat mesencephalon. This retroviral gene transduction caused no apparent changes in survival, proliferation, or differentiation. In vitro, HTH-1 gene-transduced NPCs released little l-dopa and addition of tetrahydrobiopterin, the cofactor of tyrosine hydroxylase, was required for production of l-dopa. In vivo, three of seven hemi-parkinsonian model rats that received HTH-1 gene-transduced donor NPCs achieved functional recovery. High titer retroviral vector for gene transduction could be used to prepare NPCs for transplantation to hemi-parkinsonian model rats. However, functional recovery after transplantation of HTH-1 gene-transduced NPCs was incomplete.
Kodama
Yuji
Y
Department of Molecular Neurobiology, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo. yukodama@oita-med.ac.jp
Hida
Hideki
H
Jung
Cha-Gyun
CG
Baba
Hiroko
H
Isono
Mitsuo
M
Kobayashi
Hidenori
H
Nishino
Hitoo
H
D000818:Animals; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000201:enzymology / Q000503:physiopathology / Q000601:surgery; D016332:Fetal Tissue Transplantation; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D018014:Gene Transfer Techniques; D006801:Humans; D007980:Levodopa / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology; D009474:Neurons / Q000637:transplantation* / Q000821:virology; D020734:Parkinsonian Disorders / Q000503:physiopathology / Q000601:surgery*; D051381:Rats; D017208:Rats, Wistar; D012190:Retroviridae / Q000235:genetics*; D033581:Stem Cell Transplantation / Q000379:methods*; D014161:Transduction, Genetic; D014170:Transformation, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase