Evidence map›Paper›PMID 28673774›Full record

ArticleCytotherapy2017

Development, functional characterization and validation of methodology for GMP-compliant manufacture of phagocytic macrophages: A novel cellular therapeutic for liver cirrhosis.

Alasdair R Fraser, Chloe Pass, Paul Burgoyne, Anne Atkinson, Laura Bailey, Audrey Laurie, Neil W A McGowan, Akib Hamid, Joanna K Moore, Benjamin J Dwyer and 3 more

Open access · hybridAbstract readValidation Study
In one paragraph

Article in Cytotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

30 citing papers in PubMed, 42 citations in OpenAlex.

  1. Trial
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  14. Protozoan-Derived Cytokine-Transgenic Macrophages Reverse Hepatic Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
  15. Article
  16. Article
  17. Review
  18. Macrophage cytotherapy on liver cirrhosis.Frontiers in pharmacology · 2023
    Review
  19. Article
  20. Racing CARs to veterinary immuno-oncology.Frontiers in veterinary science · 2023
    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

13 authors at 4 institutions in 1 country.

Alasdair R FraserAdvanced Therapeutics, Scottish National Blood Transfusion Service, 21 Ellen's Glen Road, Edinburgh, United Kingdom.
Chloe PassScottish National Blood Transfusion Service Cellular Therapy Development Centre, MRC Centre for Regenerative Medicine, The University of Edinburgh bioQuarter, Edinburgh, United Kingdom.
Paul BurgoyneAdvanced Therapeutics, Scottish National Blood Transfusion Service, 21 Ellen's Glen Road, Edinburgh, United Kingdom.
Anne AtkinsonScottish National Blood Transfusion Service Cellular Therapy Development Centre, MRC Centre for Regenerative Medicine, The University of Edinburgh bioQuarter, Edinburgh, United Kingdom.
Laura BaileyScottish National Blood Transfusion Service Cellular Therapy Development Centre, MRC Centre for Regenerative Medicine, The University of Edinburgh bioQuarter, Edinburgh, United Kingdom.
Audrey LaurieScottish National Blood Transfusion Service Cellular Therapy Development Centre, MRC Centre for Regenerative Medicine, The University of Edinburgh bioQuarter, Edinburgh, United Kingdom.
Neil W A McGowanScottish National Blood Transfusion Service Cellular Therapy Development Centre, MRC Centre for Regenerative Medicine, The University of Edinburgh bioQuarter, Edinburgh, United Kingdom.
Akib HamidRed Cell Integrated Laboratory, Scottish National Blood Transfusion Service, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
Joanna K MooreMRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Benjamin J DwyerMRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Marc L TurnerAdvanced Therapeutics, Scottish National Blood Transfusion Service, 21 Ellen's Glen Road, Edinburgh, United Kingdom; MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Stuart J ForbesMRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
John D M CampbellAdvanced Therapeutics, Scottish National Blood Transfusion Service, 21 Ellen's Glen Road, Edinburgh, United Kingdom; MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: johncampbell3@nhs.net.
University of Edinburgh · GBMRC Centre for Regenerative Medicine · GBScottish National Blood Transfusion Service · GBEdinburgh Royal Infirmary · GB

Funding

Medical Research Council MR/K017047/1Medical Research Council MR/M007588/1
6 · The paper itself

Abstract

BACKGROUND

aimsAutologous macrophage therapy represents a potentially significant therapeutic advance for the treatment of severe progressive liver cirrhosis. Administration of macrophages has been shown to reduce inflammation and drive fibrotic scar breakdown and tissue repair in relevant models. This therapeutic approach is being assessed for safety and feasibility in a first-in-human trial (MAcrophages Therapy for liver CirrHosis [MATCH] trial).

methodsWe outline the development and validation phases of GMP production. This includes use of the CliniMACS Prodigy cell sorting system to isolate CD14

resultsThe GMP-compliant macrophage products have a high level of purity and viability, and have a consistent phenotypic profile, expressing high levels of mature macrophage markers 25F9 and CD206 and low levels of CCR2. The macrophages demonstrate effective phagocytic capacity, are constitutively oriented to an anti-inflammatory profile and remain responsive to cytokine and TLR stimulation. The process validation shows that the cell product in excipient is remarkably robust, consistently passing the viability and phenotypic release criteria up to 48 hours after harvest.

conclusionsThis is the first report of validation of a large-scale, fully Good Manufacturing Practice-compliant, autologous macrophage cell therapy product for the potential treatment of cirrhosis. Phenotypic and functional assays confirm that these cells remain functionally viable for up to 48 h, allowing significant flexibility in administration to patients.

Indexed as

BiomarkersCell Culture TechniquesCell SeparationCell TransplantationCytokinesFemaleHumansLectins, C-TypeLipopolysaccharide ReceptorsLiver CirrhosisMacrophagesMannose-Binding LectinsMannose ReceptorMonocytesPhagocytosisReceptors, CCR2BiomarkersCCR2 protein, humanCytokinesLectins, C-TypeLipopolysaccharide ReceptorsMannose-Binding LectinsMannose ReceptorReceptors, CCR2Receptors, Cell Surfacecell therapycirrhosisGMPmacrophageprocess validation

Identifiers

PMID28673774
PMCPMC5571439
OpenAlexW2729256191

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.