Evidence map›Paper›PMID 25799576›Full record

ArticlePloS one2015

Enteric neurospheres are not specific to neural crest cultures: implications for neural stem cell therapies.

Ellen Binder, Dipa Natarajan, Julie Cooper, Rania Kronfli, Mara Cananzi, Jean-Marie Delalande, Conor McCann, Alan J Burns, Nikhil Thapar

Abstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
–field-weighted citation impact
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

27 citing papers in PubMed.

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  8. Neural crest-like stem cells for tissue regeneration.Stem cells translational medicine · 2021
    Review
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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

9 authors.

Ellen BinderStem Cells and Regenerative Medicine, UCL Institute of Child Health, London, United Kingdom.
Dipa NatarajanStem Cells and Regenerative Medicine, UCL Institute of Child Health, London, United Kingdom.
Julie CooperStem Cells and Regenerative Medicine, UCL Institute of Child Health, London, United Kingdom.
Rania KronfliStem Cells and Regenerative Medicine, UCL Institute of Child Health, London, United Kingdom.
Mara CananziStem Cells and Regenerative Medicine, UCL Institute of Child Health, London, United Kingdom.
Jean-Marie DelalandeStem Cells and Regenerative Medicine, UCL Institute of Child Health, London, United Kingdom.
Conor McCannStem Cells and Regenerative Medicine, UCL Institute of Child Health, London, United Kingdom.
Alan J BurnsStem Cells and Regenerative Medicine, UCL Institute of Child Health, London, United Kingdom; Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
Nikhil ThaparStem Cells and Regenerative Medicine, UCL Institute of Child Health, London, United Kingdom; Department of Gastroenterology, Great Ormond Street Hospital for Children, London, United Kingdom.

Funding

Medical Research Council G0800973
6 · The paper itself

Abstract

objectivesEnteric neural stem cells provide hope of curative treatment for enteric neuropathies. Current protocols for their harvesting from humans focus on the generation of 'neurospheres' from cultures of dissociated gut tissue. The study aims to better understand the derivation, generation and composition of enteric neurospheres.

designGut tissue was obtained from Wnt1-Cre;Rosa26Yfp/Yfp transgenic mice (constitutively labeled neural crest cells) and paediatric patients. Gut cells were cultured either unsorted (mixed neural crest/non-neural crest), or following FACS selection into neural crest (murine-YFP+ve/human-p75+ve) or non-neural crest (YFP-ve/p75-ve) populations. Cultures and resultant neurospheres were characterized using immunolabelling in vitro and following transplantation in vivo.

resultsCultures of (i) unsorted, (ii) neural crest, and (iii) non-neural crest cell populations generated neurospheres similar in numbers, size and morphology. Unsorted neurospheres were highly heterogeneous for neural crest content. Neural crest-derived (YFP+ve/p75+ve) neurospheres contained only neural derivatives (neurons and glia) and were devoid of non-neural cells (i.e. negative for SMA, c-Kit), with the converse true for non-neural crest-derived (YFP-ve/p75-ve) 'neurospheres'. Under differentiation conditions only YFP+ve cells gave rise to neural derivatives. Both YFP+ve and YFP-ve cells displayed proliferation and spread upon transplantation in vivo, but YFP-ve cells did not locate or integrate within the host ENS.

conclusionsSpherical accumulations of cells, so-called 'neurospheres' forming in cultures of dissociated gut contain variable proportions of neural crest-derived cells. If they are to be used for ENS cell replacement therapy then improved protocols for their generation, including cell selection, should be sought in order to avoid inadvertent transplantation of non-therapeutic, non-ENS cells.

Indexed as

Cell- and Tissue-Based TherapyCell DifferentiationAnimalsBacterial ProteinsCells, CulturedEnteric Nervous SystemFemaleGastrointestinal TractHumansLuminescent ProteinsMaleMiceMice, TransgenicNeural CrestNeural Stem CellsWnt1 ProteinBacterial ProteinsLuminescent ProteinsWnt1 ProteinWnt1 protein, mouseyellow fluorescent protein, Bacteria

Identifiers

PMID25799576
PMCPMC4370605

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Registered trials

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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.