Evidence map›Paper›PMID 27243814›Full record

ArticlePloS one2016

Generation of Functional Beta-Like Cells from Human Exocrine Pancreas.

Maria J Lima, Kenneth R Muir, Hilary M Docherty, Neil W A McGowan, Shareen Forbes, Yves Heremans, Harry Heimberg, John Casey, Kevin Docherty

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
5.0field-weighted citation impact, top 5% 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

20 citing papers in PubMed, 44 citations in OpenAlex.

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  18. [Research progress on the donor cell sources of pancreatic islet transplantation for treatment of diabetes mellitus].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2018
    Review
  19. Review
  20. Regenerative medicine and cell-based approaches to restore pancreatic function.Nature reviews. Gastroenterology & hepatology · 2017
    Review
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 at 4 institutions in 2 countries.

Maria J LimaSchool of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom.
Kenneth R MuirSchool of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom.
Hilary M DochertySchool of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom.
Neil W A McGowanDepartment of Surgery, University of Edinburgh, Edinburgh Royal Infirmary, Edinburgh, EH16 4SU, United Kingdom.
Shareen ForbesEndocrinology Unit, University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, United Kingdom.
Yves HeremansDiabetes Research Centre, Vrije Universiteit Brussel, B1090 Brussels, Belgium.
Harry HeimbergDiabetes Research Centre, Vrije Universiteit Brussel, B1090 Brussels, Belgium.
John CaseyDepartment of Surgery, University of Edinburgh, Edinburgh Royal Infirmary, Edinburgh, EH16 4SU, United Kingdom.
Kevin DochertySchool of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom.
University of Aberdeen · GBUniversity of Edinburgh · GBVrije Universiteit Brussel · BEEdinburgh Royal Infirmary · GB

Funding

Medical Research Council J015377/1Medical Research Council MR/J015377/1Wellcome Trust
6 · The paper itself

Abstract

Transcription factor mediated lineage reprogramming of human pancreatic exocrine tissue could conceivably provide an unlimited supply of islets for transplantation in the treatment of diabetes. Exocrine tissue can be efficiently reprogrammed to islet-like cells using a cocktail of transcription factors: Pdx1, Ngn3, MafA and Pax4 in combination with growth factors. We show here that overexpression of exogenous Pax4 in combination with suppression of the endogenous transcription factor ARX considerably enhances the production of functional insulin-secreting β-like cells with concomitant suppression of α-cells. The efficiency was further increased by culture on laminin-coated plates in media containing low glucose concentrations. Immunocytochemistry revealed that reprogrammed cultures were composed of ~45% islet-like clusters comprising >80% monohormonal insulin+ cells. The resultant β-like cells expressed insulin protein levels at ~15-30% of that in adult human islets, efficiently processed proinsulin and packaged insulin into secretory granules, exhibited glucose responsive insulin secretion, and had an immediate and prolonged effect in normalising blood glucose levels upon transplantation into diabetic mice. We estimate that approximately 3 billion of these cells would have an immediate therapeutic effect following engraftment in type 1 diabetes patients and that one pancreas would provide sufficient tissue for numerous transplants.

Indexed as

AdultAnimalsCell- and Tissue-Based TherapyCells, CulturedCellular Reprogramming TechniquesDiabetes Mellitus, ExperimentalFemaleGlucoseHomeodomain ProteinsHumansInsulinInsulin-Secreting CellsMaleMiceMice, SCIDPaired Box Transcription FactorsARX protein, humanGlucoseHomeodomain ProteinsInsulinPaired Box Transcription FactorsPAX4 protein, humanProinsulinRNA, Small InterferingStreptozocinTranscription Factors

Identifiers

PMID27243814
PMCPMC4887015
OpenAlexW2414175118

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.