Evidence map›Paper›PMID 31698463›Full record

ArticleBlood advances2019

Large-scale in vitro production of red blood cells from human peripheral blood mononuclear cells.

Steven Heshusius, Esther Heideveld, Patrick Burger, Marijke Thiel-Valkhof, Erica Sellink, Eszter Varga, Elina Ovchynnikova, Anna Visser, Joost H A Martens, Marieke von Lindern and 1 more

Open access · goldAbstract read
In one paragraph

Article in Blood advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
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

56 citing papers in PubMed, 95 citations in OpenAlex.

  1. Article
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  3. Blood Pharming of Red Cells.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2026
    Review
  4. Article
  5. Red blood cell-derived transglutaminase 2 influences thrombus formation.Research and practice in thrombosis and haemostasis · 2026
    Article
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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

11 authors at 3 institutions in 1 country.

Steven HeshusiusSanquin Research, Department of Hematopoiesis and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Esther HeideveldSanquin Research, Department of Hematopoiesis and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Patrick BurgerSanquin Research, Department of Hematopoiesis and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Marijke Thiel-ValkhofLaboratory for Cell Therapy, Sanquin Research, Amsterdam, The Netherlands; and.
Erica SellinkLaboratory for Cell Therapy, Sanquin Research, Amsterdam, The Netherlands; and.
Eszter VargaSanquin Research, Department of Hematopoiesis and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Elina OvchynnikovaSanquin Research, Department of Hematopoiesis and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Anna VisserSanquin Research, Department of Hematopoiesis and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Joost H A MartensDepartment of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.
Marieke von LindernSanquin Research, Department of Hematopoiesis and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Emile van den AkkerSanquin Research, Department of Hematopoiesis and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Sanquin · NLErasmus MC · NLRadboud University Nijmegen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Transfusion of donor-derived red blood cells (RBC) is the most common form of cellular therapy. Donor availability and the potential risk of alloimmunization and other transfusion-related complications may, however, limit the availability of transfusion units, especially for chronically transfused patients. In vitro cultured, customizable RBC would negate these concerns and further increase precision medicine. Large-scale, cost-effective production depends on optimization of culture conditions. We developed a defined medium and adapted our protocols to good manufacturing practice (GMP) culture requirements, which reproducibly provided pure erythroid cultures from peripheral blood mononuclear cells without prior CD34+ isolation, and a 3 × 107-fold increase in erythroblasts in 25 days (or from 100 million peripheral blood mononuclear cells, 2 to 4 mL packed red cells can be produced). Expanded erythroblast cultures could be differentiated to CD71dimCD235a+CD44+CD117-DRAQ5- RBC in 12 days. More than 90% of the cells enucleated and expressed adult hemoglobin as well as the correct blood group antigens. Deformability and oxygen-binding capacity of cultured RBC was comparable to in vivo reticulocytes. Daily RNA sampling during differentiation followed by RNA-sequencing provided a high-resolution map/resource of changes occurring during terminal erythropoiesis. The culture process was compatible with upscaling using a G-Rex bioreactor with a capacity of 1 L per reactor, allowing transition toward clinical studies and small-scale applications.

Indexed as

Batch Cell Culture TechniquesCell DifferentiationErythropoiesisBiomarkersBioreactorsCell ProliferationErythroblastsErythrocytesGene Expression ProfilingHumansImmunophenotypingLeukocytes, MononuclearPrimary Cell CultureReticulocytesTranscriptomeBiomarkers

Identifiers

PMID31698463
PMCPMC6855111
OpenAlexW2988637016

What Socratic 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 Socratic graph.