Evidence map›Paper›PMID 18388307›Full record

ArticleStem cells (Dayton, Ohio)2008

Embryonic stem cell-derived Pitx3-enhanced green fluorescent protein midbrain dopamine neurons survive enrichment by fluorescence-activated cell sorting and function in an animal model of Parkinson's disease.

Eva Hedlund, Jan Pruszak, Thomas Lardaro, Wesley Ludwig, Angel Viñuela, Kwang-Soo Kim, Ole Isacson

Open access · bronzeAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 1 pooled it
7.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. On the Road from Phenotypic Plasticity to Stem Cell Therapy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Treatment of Parkinson's disease using cell transplantation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2015
    Review
  19. Direct somatic lineage conversion.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2015
    Review
  20. Sorting the wheat from the chaff in dopamine neuron-based cell therapies.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article

2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Eva HedlundUdall Parkinson's Disease Research Center for Excellence, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA.
Jan Pruszak
Thomas Lardaro
Wesley Ludwig
Angel Viñuela
Kwang-Soo Kim
Ole Isacson
Harvard University · USMcLean Hospital · US

Funding

Transplantation of ES Cell-derived DA Neurons into PD Primate ModelsP50NS039793 · NINDS · MC LEAN HOSPITAL (BELMONT, MA) · PI ISACSON, OLE · 1999 to 2010
$16.3M
Functional Roles of Nurr1 for Midbrain Dopamine Neurons in Health and DiseaseR01NS084869 · NINDS · MCLEAN HOSPITAL · PI KIM, KWANG-SOO · 2014 to 2018
$1.7M
NINDS NIH HHS P50 NS039793NINDS NIH HHS P50 NS39793NINDS NIH HHS R01 NS084869PHS HHS 48866
6 · The paper itself

Abstract

Both fetal ventral mesencephalic (VM) and embryonic stem (ES) cell-derived dopamine neurons have been used successfully to correct behavioral responses in animal models of Parkinson's disease. However, grafts derived from fetal VM cells or from ES cells contain multiple cell types, and the majority of these cells are not dopamine neurons. Isolation of ES cell-derived dopamine neurons and subsequent transplantation would both elucidate the capacity of these neurons to provide functional input and also further explore an efficient and safer use of ES cells for the treatment of Parkinson's disease. Toward this goal, we used a Pitx3-enhanced green fluorescent protein (Pitx3-eGFP) knock-in mouse blastocyst-derived embryonic stem (mES) cell line and fluorescence-activated cell sorting (FACS) to select and purify midbrain dopamine neurons. Initially, the dopaminergic marker profile of intact Pitx3-eGFP mES cultures was evaluated after differentiation in vitro. eGFP expression overlapped closely with that of Pitx3, Nurr1, Engrailed-1, Lmx1a, tyrosine hydroxylase (TH), l-aromatic amino acid decarboxylase (AADC), and vesicular monoamine transporter 2 (VMAT2), demonstrating that these cells were of a midbrain dopamine neuron character. Furthermore, postmitotic Pitx3-eGFP(+) dopamine neurons, which constituted 2%-5% of all live cells in the culture after dissociation, could be highly enriched to >90% purity by FACS, and these isolated neurons were viable, extended neurites, and maintained a dopaminergic profile in vitro. Transplantation to 6-hydroxydopamine-lesioned rats showed that an enriched dopaminergic population could survive and restore both amphetamine- and apomorphine-induced functions, and the grafts contained large numbers of midbrain dopamine neurons, which innervated the host striatum. Disclosure of potential conflicts of interest is found at the end of this article.

Indexed as

AmphetamineAnimalsApomorphineCell DifferentiationCell SurvivalEmbryonic Stem CellsFlow CytometryGenes, ReporterGreen Fluorescent ProteinsHomeodomain ProteinsHydroxydopaminesMesencephalonMiceMitosisMotor ActivityParkinsonian Disorders5-hydroxydopamineAmphetamineApomorphineGreen Fluorescent Proteinshomeobox protein PITX3Homeodomain ProteinsHydroxydopaminesTranscription Factors

Identifiers

PMID18388307
PMCPMC2693914
OpenAlexW2040366241

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.