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 | |
| Publication status | Published - 18-04-2007 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Developmental Biology
- Cell Biology
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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 journal › Article
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 -