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

doi:10.1634/stemcells.2006-0386

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 journal › Article › peer-review

114 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 language	English
Pages (from-to)	918-928
Number of pages	11
Journal	Stem Cells
Volume	25
Issue number	4
DOIs	https://doi.org/10.1634/stemcells.2006-0386
Publication status	Published - 2007
Externally published	Yes

All Science Journal Classification (ASJC) codes

Molecular Medicine
Developmental Biology
Cell Biology

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Rodríguez-Gómez, J. A., Lu, J. Q., Velasco, I., Rivera, S., Zoghbi, S. S., Liow, J. S., Musachio, J. L., Chin, F. T., Toyama, H., Seidel, J., Green, M. V., Thanos, P. K., Ichise, M., Pike, V. W., Innis, R. B., & 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.

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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.",

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year = "2007",

doi = "10.1634/stemcells.2006-0386",

language = "English",

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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, 2007, p. 918-928.

Research output: Contribution to journal › Article › peer-review

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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

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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.

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