Human induced pluripotent stem cell-derived neurons improve motor asymmetry in a 6-hydroxydopamine-induced rat model of Parkinson's disease.
OBJECTIVE
Since human embryonic stem cells and human fetal neural stem cells have immune rejection and ethical issues, recent advancements in induced pluripotent stem cells (iPS cells) provide new possibilities to study autologous cell therapy for Parkinson's disease (PD).


METHODS
We isolated human skin fibroblasts from normal individuals and patients with PD; we generated iPS cells by transfecting these human skin fibroblasts with retroviral reprogramming factors of OCT4, SOX2, KLF4 and c-MYC and induced iPS cells to differentiate neural stem cells (NSCs) and then into neurons and dopamine neurons in vitro.


RESULTS
We found that iPS cell-derived NSC transplant into the striatum of the 6-hydroxydopamine (OHDA)-induced PD rats improved their functional defects of rotational asymmetry at 4, 8, 12 and 16 weeks after transplantation. iPS cell-derived NSCs were found to survive and integrate into the brain of transplanted PD rats and differentiated into neurons, including dopamine neurons in vivo.


CONCLUSIONS
Transplantation of iPS cell-derived NSCs has therapeutic potential for PD. Our study provided experimental proof for future clinical application of iPS cells in cell-based treatment of PD.
Centre for Stem Cells and Regenerative Medicine, The Liaocheng People's Hospital/Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, China. Electronic address: Fhan2013@126.com.
Fabin
F
Han
Centre for Stem Cells and Regenerative Medicine, The Liaocheng People's Hospital/Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, China.
Wei
W
Wang
Centre for Stem Cells and Regenerative Medicine, The Liaocheng People's Hospital/Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, China.
Baoxing
B
Chen
Centre for Stem Cells and Regenerative Medicine, The Liaocheng People's Hospital/Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, China.
Chao
C
Chen
Centre for Stem Cells and Regenerative Medicine, The Liaocheng People's Hospital/Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, China.
Sen
S
Li
Centre for Stem Cells and Regenerative Medicine, The Liaocheng People's Hospital/Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, China.
Xianjie
X
Lu
Centre for Stem Cells and Regenerative Medicine, The Liaocheng People's Hospital/Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, China.
Jing
J
Duan
Centre for Stem Cells and Regenerative Medicine, The Liaocheng People's Hospital/Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, China.
Yang
Y
Zhang
Centre for Cell Therapy, Xuanwu Hospital, Capital Medical University, Beijing, China.
Yu Alex
YA
Zhang
Centre for Stem Cells and Regenerative Medicine, The Liaocheng People's Hospital/Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, China.
Wennian
W
Guo
Centre for Stem Cells and Regenerative Medicine, The Liaocheng People's Hospital/Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, China.
Guangyao
G
Li
D000368:Aged; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D000090062:Kruppel-Like Factor 4; D008297:Male; D051379:Mice; D008875:Middle Aged; D009046:Motor Neurons / Q000166:cytology*; D058953:Neural Stem Cells / Q000166:cytology; D016627:Oxidopamine; D010300:Parkinson Disease / Q000473:pathology / Q000628:therapy*; D039904:Pluripotent Stem Cells / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000473:pathology; D033581:Stem Cell Transplantation; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; C000715469:Klf4 protein, rat; D000090062:Kruppel-Like Factor 4; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase
Parkinson's disease; differentiation; dopamine neuron; iPS cell; neural stem cell; transplantation