Persistent dopamine functions of neurons derived from embryonic stem cells in a rodent model of parkinson disease

Jose A. Rodríguez-Gómez, Jian Qiang Lu, Iván Velasco, Seth Rivera, Sami S. Zoghbi, Jeih San Liow, John L. Musachio, Frederick T. Chin, Hiroshi Toyama, Jurgen Seidel, Michael V. Green, Panayotis K. Thanos, Masanori Ichise, Victor W. Pike, Robert B. Innis, Ron D.G. Mckay

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

The derivation of dopamine neurons is one of the best examples of the clinical potential of embryonic stem (ES) cells, but the long-term function of the grafted neurons has not been established. Here, we show that, after transplantation into an animal model, neurons derived from mouse ES cells survived for over 32 weeks, maintained midbrain markers, and had sustained behavioral effects. Microdialysis in grafted animals showed that dopamine (DA) release was induced by depolarization and pharmacological stimulants. Positron emission tomography measured the expression of presynaptic dopamine transporters in the graft and also showed that the number of postsynaptic DA D2 receptors was normalized in the host striatum. These data suggest that ES cell-derived neurons show DA release and reuptake and stimulate appropriate postsynaptic responses for long periods after implantation. This work supports continued interest in ES cells as a source of functional DA neurons.

Original languageEnglish
Pages (from-to)918-928
Number of pages11
JournalStem Cells
Volume25
Issue number4
DOIs
Publication statusPublished - 18-04-2007
Externally publishedYes

Fingerprint

Dopaminergic Neurons
Embryonic Stem Cells
Parkinson Disease
Rodentia
Neurons
Dopamine Plasma Membrane Transport Proteins
Dopamine D2 Receptors
Microdialysis
Mesencephalon
Positron-Emission Tomography
Dopamine
Animal Models
Transplantation
Pharmacology
Transplants

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Rodríguez-Gómez, J. A., Lu, J. Q., Velasco, I., Rivera, S., Zoghbi, S. S., Liow, J. S., ... Mckay, R. D. G. (2007). Persistent dopamine functions of neurons derived from embryonic stem cells in a rodent model of parkinson disease. Stem Cells, 25(4), 918-928. https://doi.org/10.1634/stemcells.2006-0386
Rodríguez-Gómez, Jose A. ; Lu, Jian Qiang ; Velasco, Iván ; Rivera, Seth ; Zoghbi, Sami S. ; Liow, Jeih San ; Musachio, John L. ; Chin, Frederick T. ; Toyama, Hiroshi ; Seidel, Jurgen ; Green, Michael V. ; Thanos, Panayotis K. ; Ichise, Masanori ; Pike, Victor W. ; Innis, Robert B. ; Mckay, Ron D.G. / Persistent dopamine functions of neurons derived from embryonic stem cells in a rodent model of parkinson disease. In: Stem Cells. 2007 ; Vol. 25, No. 4. pp. 918-928.
@article{5ae3b63675a04b05bb3463988daeb037,
title = "Persistent dopamine functions of neurons derived from embryonic stem cells in a rodent model of parkinson disease",
abstract = "The derivation of dopamine neurons is one of the best examples of the clinical potential of embryonic stem (ES) cells, but the long-term function of the grafted neurons has not been established. Here, we show that, after transplantation into an animal model, neurons derived from mouse ES cells survived for over 32 weeks, maintained midbrain markers, and had sustained behavioral effects. Microdialysis in grafted animals showed that dopamine (DA) release was induced by depolarization and pharmacological stimulants. Positron emission tomography measured the expression of presynaptic dopamine transporters in the graft and also showed that the number of postsynaptic DA D2 receptors was normalized in the host striatum. These data suggest that ES cell-derived neurons show DA release and reuptake and stimulate appropriate postsynaptic responses for long periods after implantation. This work supports continued interest in ES cells as a source of functional DA neurons.",
author = "Rodr{\'i}guez-G{\'o}mez, {Jose A.} and Lu, {Jian Qiang} and Iv{\'a}n Velasco and Seth Rivera and Zoghbi, {Sami S.} and Liow, {Jeih San} and Musachio, {John L.} and Chin, {Frederick T.} and Hiroshi Toyama and Jurgen Seidel and Green, {Michael V.} and Thanos, {Panayotis K.} and Masanori Ichise and Pike, {Victor W.} and Innis, {Robert B.} and Mckay, {Ron D.G.}",
year = "2007",
month = "4",
day = "18",
doi = "10.1634/stemcells.2006-0386",
language = "English",
volume = "25",
pages = "918--928",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "AlphaMed Press",
number = "4",

}

Rodríguez-Gómez, JA, Lu, JQ, Velasco, I, Rivera, S, Zoghbi, SS, Liow, JS, Musachio, JL, Chin, FT, Toyama, H, Seidel, J, Green, MV, Thanos, PK, Ichise, M, Pike, VW, Innis, RB & Mckay, RDG 2007, 'Persistent dopamine functions of neurons derived from embryonic stem cells in a rodent model of parkinson disease', Stem Cells, vol. 25, no. 4, pp. 918-928. https://doi.org/10.1634/stemcells.2006-0386

Persistent dopamine functions of neurons derived from embryonic stem cells in a rodent model of parkinson disease. / Rodríguez-Gómez, Jose A.; Lu, Jian Qiang; Velasco, Iván; Rivera, Seth; Zoghbi, Sami S.; Liow, Jeih San; Musachio, John L.; Chin, Frederick T.; Toyama, Hiroshi; Seidel, Jurgen; Green, Michael V.; Thanos, Panayotis K.; Ichise, Masanori; Pike, Victor W.; Innis, Robert B.; Mckay, Ron D.G.

In: Stem Cells, Vol. 25, No. 4, 18.04.2007, p. 918-928.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Persistent dopamine functions of neurons derived from embryonic stem cells in a rodent model of parkinson disease

AU - Rodríguez-Gómez, Jose A.

AU - Lu, Jian Qiang

AU - Velasco, Iván

AU - Rivera, Seth

AU - Zoghbi, Sami S.

AU - Liow, Jeih San

AU - Musachio, John L.

AU - Chin, Frederick T.

AU - Toyama, Hiroshi

AU - Seidel, Jurgen

AU - Green, Michael V.

AU - Thanos, Panayotis K.

AU - Ichise, Masanori

AU - Pike, Victor W.

AU - Innis, Robert B.

AU - Mckay, Ron D.G.

PY - 2007/4/18

Y1 - 2007/4/18

N2 - The derivation of dopamine neurons is one of the best examples of the clinical potential of embryonic stem (ES) cells, but the long-term function of the grafted neurons has not been established. Here, we show that, after transplantation into an animal model, neurons derived from mouse ES cells survived for over 32 weeks, maintained midbrain markers, and had sustained behavioral effects. Microdialysis in grafted animals showed that dopamine (DA) release was induced by depolarization and pharmacological stimulants. Positron emission tomography measured the expression of presynaptic dopamine transporters in the graft and also showed that the number of postsynaptic DA D2 receptors was normalized in the host striatum. These data suggest that ES cell-derived neurons show DA release and reuptake and stimulate appropriate postsynaptic responses for long periods after implantation. This work supports continued interest in ES cells as a source of functional DA neurons.

AB - The derivation of dopamine neurons is one of the best examples of the clinical potential of embryonic stem (ES) cells, but the long-term function of the grafted neurons has not been established. Here, we show that, after transplantation into an animal model, neurons derived from mouse ES cells survived for over 32 weeks, maintained midbrain markers, and had sustained behavioral effects. Microdialysis in grafted animals showed that dopamine (DA) release was induced by depolarization and pharmacological stimulants. Positron emission tomography measured the expression of presynaptic dopamine transporters in the graft and also showed that the number of postsynaptic DA D2 receptors was normalized in the host striatum. These data suggest that ES cell-derived neurons show DA release and reuptake and stimulate appropriate postsynaptic responses for long periods after implantation. This work supports continued interest in ES cells as a source of functional DA neurons.

UR - http://www.scopus.com/inward/record.url?scp=34147180060&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34147180060&partnerID=8YFLogxK

U2 - 10.1634/stemcells.2006-0386

DO - 10.1634/stemcells.2006-0386

M3 - Article

C2 - 17170065

AN - SCOPUS:34147180060

VL - 25

SP - 918

EP - 928

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

IS - 4

ER -