Distinct efficacy of pre-differentiated versus intact fetal mesencephalon-derived human neural progenitor cells in alleviating rat model of Parkinson's disease.
Neural progenitor cells have shown the effectiveness in the treatment of Parkinson's disease, but the therapeutic efficacy remains variable. One of important factors that determine the efficacy is the necessity of pre-differentiation of progenitor cells into dopaminergic neurons before transplantation. This study therefore investigated the therapeutic efficacy of mesencephalon-derived human neural progenitor cells with or without the pre-differentiation in alleviating a rat model of Parkinson's disease. We found that a combination of 50 ng/ml fibroblast growth factor 8, 10 ng/ml glial cell line-derived neurotrophic factor and 10 microM forskolin facilitated the differentiation of human fetal mesencephalic progenitor cells into dopaminergic neurons in vitro. More importantly, after transplanted into the striatum of parkinsonian rats, only pre-differentiated grafts resulted in an elevated production of dopamine in the transplanted site and the amelioration of behavioral impairments of the parkinsonian rats. Unlike pre-differentiated progenitors, grafted intact progenitors rarely differentiated into dopaminergic neurons in vivo and emigrated actively away from the transplanted site. These data demonstrates the importance of pre-differentiation of human progenitor cells before transplantation in enhancing therapeutic potency for Parkinson's disease.
Wang
Xuan
X
Neuroscience Research Institute, Peking University, 38# Xueyuan Road, Beijing 100083, PR China.
Lu
Yanyan
Y
Zhang
Huanqing
H
Wang
Kun
K
He
Qihua
Q
Wang
Yue
Y
Liu
Xianyu
X
Li
Linsong
L
Wang
Xiaomin
X
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D001522:Behavior, Animal; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism / Q000637:transplantation; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis; D004622:Embryo, Mammalian; D005260:Female; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology*; D009414:Nerve Growth Factors / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology / Q000637:transplantation*; D010300:Parkinson Disease / Q000628:therapy*; D051381:Rats; D020127:Recovery of Function / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C496456:FGF8 protein, human; C496458:Fgf8 protein, rat; C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D019394:Ki-67 Antigen; C577484:NES protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D016900:Neurofilament Proteins; D015102:3,4-Dihydroxyphenylacetic Acid; C061195:neurofilament protein M; D051524:Fibroblast Growth Factor 8; D005576:Colforsin; D005346:Fibroblast Growth Factors; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine