Transplanted dopamine neurons derived from primate ES cells preferentially innervate DARPP-32 striatal progenitors within the graft.

Transplanted dopamine neurons derived from primate ES cells preferentially innervate DARPP-32 striatal progenitors within the graft. Research Abstract Details 

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Transplanted dopamine neurons derived from primate ES cells preferentially innervate DARPP-32 striatal progenitors within the graft. Abstract Text:

Daniela Ferrari,Rosario Sanchez-Pernaute,Hyojin Lee,Lorenz Studer,Ole Isacson,

The correct identity and functional capacity of transplanted dopamine (DA) neurons derived in vitro from embryonic stem (ES) cells is a critical factor for the development of an ES cell-based replacement therapy for Parkinson's disease. We transplanted primate Cyno-1 ES cells differentiated in vitro for 4 (progenitor ES cells) or 6 (differentiated ES cells) weeks, or control fetal primate cells into the striatum of hemi-parkinsonian rats. Partial behavioral recovery in amphetamine-induced rotation was correlated with the number of ES-derived tyrosine hydroxylase-positive (TH+) neurons in the grafts (r=0.5, P<0.05). Post mortem analysis of ES-derived grafts revealed TH+neurons with mature morphology, similar to fetal DA neurons, and expression of midbrain transcription factors, such as Engrailed (En) and Nurr-1. While the total number of TH+neurons was not different between the two groups, TH/En co-expression was significantly higher (>90%) in grafts from differentiated ES cells than in grafts derived from progenitor cells (<50%), reflecting a more heterogeneous cellular composition. Within the grafts there was an overlap between ES-derived TH+axonal arbors and clusters of primate ES-derived striatal neurons expressing brain factor 1 (Bf-1, Foxg1) and DA and cAMP-regulated phosphoprotein (DARPP-32). Such overlap was never observed for other regional transcription factors that define neighboring forebrain domains in the developing brain, such as Nkx2.1 (medial ganglionic eminence), Nkx2.2 (pallidal and diencephalic progenitors) or Pax6 (dorsal telencephalic progenitors). Despite the heterogeneity of ES-derived graft cell composition, these results demonstrate normal phenotypic specification, conserved natural axonal target selectivity and functionality of DA neurons derived from primate ES cells.

Transplanted dopamine neurons derived from primate ES cells preferentially innervate DARPP-32 striatal progenitors within the graft. Publishing Authors By Initials

D Ferrari,R Sanchez-Pernaute,H Lee,L Studer,O Isacson,

For similar proteins: carrier proteins: membrane transport proteins: ion pumps: antiporters: vesicular neurotransmitter transport proteins: vesicular biogenic amine transport proteins: vesicular monoamine transport proteins research abstracts see: proteins: carrier proteins: membrane transport proteins: ion pumps: antiporters: vesicular neurotransmitter transport proteins: vesicular biogenic amine transport proteins: vesicular monoamine transport proteins research

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Transplanted dopamine neurons derived from primate ES cells preferentially innervate DARPP-32 striatal progenitors within the graft. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The European journal of neuroscience

VOLUME: 24

Page Numbers: 1885-96

Journal Abbreviation: Eur. J. Neurosci.

ISSN: 0953-816X

DAY: 3

MONTH: Oct

YEAR: 2006

Transplanted dopamine neurons derived from primate ES cells preferentially innervate DARPP-32 striatal progenitors within the graft. Information

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LANGUAGE: eng

NlmUniqueID: 8918110

Transplanted dopamine neurons derived from primate ES cells preferentially innervate DARPP-32 striatal progenitors within the graft. Keywords Mesh Terms:

KEYWORDS: Vesicular Monoamine Transport Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: Transplanted dopamine neurons derived from primate ES cells preferentially innervate DARPP-32 striatal progenitors within the graft. Information

Substance Name: Tyrosine 3-Monooxygenase

Registry Number: EC 1.14.16.2

Grant and Affiliation Information for Transplanted dopamine neurons derived from primate ES cells preferentially innervate DARPP-32 striatal progenitors within the graft.

AFFILIATION: McLean Hospital/Harvard University Udall Parkinson's Disease Research Center of Excellence, 115 Mill St, Belmont, MA 02478, USA.

Country: France

AGENCY: United States NCRR

GRANT: P51RR00168

ACRONYM: RR

MEDLINETA: Eur J Neurosci

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