Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells

Soo Cho Myung, Young Eun Lee, Young Kim Ji, Seungsoo Chung, Hee Cho Yoon, Dae Sung Kim, Sang Moon Kang, Haksup Lee, Myung Hwa Kim, Jeong Hoon Kim, Woo Leem Joong, Kyung Oh Sun, Min Choi Young, Dong Youn Hwang, Woo Chang Jin, Dong Wook Kim

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)3392-3397
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number9
DOIs
Publication statusPublished - 2008 Mar 4

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Dopaminergic Neurons
Feeder Cells
Neurons
Tyrosine 3-Monooxygenase
Cell- and Tissue-Based Therapy
Human Embryonic Stem Cells
Neoplasms

All Science Journal Classification (ASJC) codes

  • General

Cite this

Myung, Soo Cho ; Lee, Young Eun ; Ji, Young Kim ; Chung, Seungsoo ; Yoon, Hee Cho ; Kim, Dae Sung ; Kang, Sang Moon ; Lee, Haksup ; Kim, Myung Hwa ; Kim, Jeong Hoon ; Joong, Woo Leem ; Sun, Kyung Oh ; Young, Min Choi ; Hwang, Dong Youn ; Jin, Woo Chang ; Kim, Dong Wook. / Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 9. pp. 3392-3397.
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title = "Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells",
abstract = "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.",
author = "Myung, {Soo Cho} and Lee, {Young Eun} and Ji, {Young Kim} and Seungsoo Chung and Yoon, {Hee Cho} and Kim, {Dae Sung} and Kang, {Sang Moon} and Haksup Lee and Kim, {Myung Hwa} and Kim, {Jeong Hoon} and Joong, {Woo Leem} and Sun, {Kyung Oh} and Young, {Min Choi} and Hwang, {Dong Youn} and Jin, {Woo Chang} and Kim, {Dong Wook}",
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month = "3",
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doi = "10.1073/pnas.0712359105",
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Myung, SC, Lee, YE, Ji, YK, Chung, S, Yoon, HC, Kim, DS, Kang, SM, Lee, H, Kim, MH, Kim, JH, Joong, WL, Sun, KO, Young, MC, Hwang, DY, Jin, WC & Kim, DW 2008, 'Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells', Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 9, pp. 3392-3397. https://doi.org/10.1073/pnas.0712359105

Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells. / Myung, Soo Cho; Lee, Young Eun; Ji, Young Kim; Chung, Seungsoo; Yoon, Hee Cho; Kim, Dae Sung; Kang, Sang Moon; Lee, Haksup; Kim, Myung Hwa; Kim, Jeong Hoon; Joong, Woo Leem; Sun, Kyung Oh; Young, Min Choi; Hwang, Dong Youn; Jin, Woo Chang; Kim, Dong Wook.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 9, 04.03.2008, p. 3392-3397.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells

AU - Myung, Soo Cho

AU - Lee, Young Eun

AU - Ji, Young Kim

AU - Chung, Seungsoo

AU - Yoon, Hee Cho

AU - Kim, Dae Sung

AU - Kang, Sang Moon

AU - Lee, Haksup

AU - Kim, Myung Hwa

AU - Kim, Jeong Hoon

AU - Joong, Woo Leem

AU - Sun, Kyung Oh

AU - Young, Min Choi

AU - Hwang, Dong Youn

AU - Jin, Woo Chang

AU - Kim, Dong Wook

PY - 2008/3/4

Y1 - 2008/3/4

N2 - 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.

AB - 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.

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DO - 10.1073/pnas.0712359105

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