Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells.
We developed a method for the efficient generation of functional dopaminergic (DA) neurons from human embryonic stem cells (hESCs) on a large scale. The most unique feature of this method is the generation of homogeneous spherical neural masses (SNMs) from the hESC-derived neural precursors. These SNMs provide several advantages: (i) they can be passaged for a long time without losing their differentiation capability into DA neurons; (ii) they can be coaxed into DA neurons at much higher efficiency than that from previous reports (86% tyrosine hydroxylase-positive neurons/total neurons); (iii) the induction of DA neurons from SNMs only takes 14 days; and (iv) no feeder cells are required during differentiation. These advantages allowed us to obtain a large number of DA neurons within a short time period and minimized potential contamination of unwanted cells or pathogens coming from the feeder layer. The highly efficient differentiation may not only enhance the efficacy of the cell therapy but also reduce the potential tumor formation from the undifferentiated residual hESCs. In line with this effect, we have never observed any tumor formation from the transplanted animals used in our study. When grafted into a parkinsonian rat model, the hESC-derived DA neurons elicited clear behavioral recovery in three behavioral tests. In summary, our study paves the way for the large-scale generation of purer and functional DA neurons for future clinical applications.
Cho
Myung Soo
MS
Research and Development Center, Jeil Pharmaceutical Co., Ltd., Yongin 449-861, Korea.
Lee
Young-Eun
YE
Kim
Ji Young
JY
Chung
Seungsoo
S
Cho
Yoon Hee
YH
Kim
Dae-Sung
DS
Kang
Sang-Moon
SM
Lee
Haksup
H
Kim
Myung-Hwa
MH
Kim
Jeong-Hoon
JH
Leem
Joong Woo
JW
Oh
Sun Kyung
SK
Choi
Young Min
YM
Hwang
Dong-Youn
DY
Chang
Jin Woo
JW
Kim
Dong-Wook
DW
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D017690:Cell Transplantation; D004195:Disease Models, Animal; D004298:Dopamine; D053595:Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D008722:Methods; D009474:Neurons / Q000166:cytology* / Q000637:transplantation*; D010300:Parkinson Disease / Q000628:therapy; D051381:Rats
D004298:Dopamine