Evidence map›Paper›PMID 38886860›Full record

ArticleStem cell research & therapy2024

Standardized generation of human iPSC-derived hematopoietic organoids and macrophages utilizing a benchtop bioreactor platform under fully defined conditions.

Mania Ackermann, Fawaz Saleh, Shifaa M Abdin, Anna Rafiei Hashtchin, Ingrid Gensch, Julia Golgath, Marco Carvalho Oliveira, Ariane H H Nguyen, Svenja Gaedcke, Arno Fenske and 5 more

Abstract read
In one paragraph

Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. CAR-engineered neutrophils derived from induced pluripotent stem cells: a new frontier in cellular immunotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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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

15 authors.

Mania Ackermann *Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
Fawaz Saleh *Department for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, Germany.
Shifaa M Abdin *Department for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, Germany.
Anna Rafiei HashtchinDepartment for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, Germany.
Ingrid GenschFraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
Julia GolgathFraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
Marco Carvalho OliveiraDepartment for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, Germany.
Ariane H H NguyenDepartment for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, Germany.
Svenja GaedckeBiomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover Medical School, Hannover, Germany.
Arno FenskeInstitute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
Mi-Sun JangDepartment for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, Germany.
Adan C JirmoDepartment for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, Germany.
Markus AbelnInstitute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
Gesine HansenDepartment for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, Germany.
Nico LachmannFraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany. Lachmann.nico@mh-hannover.de.ORCID http://orcid.org/0000-0002-4245-1497

Funding

Deutsche Forschungsgemeinschaft LA 3680/9-1HORIZON EUROPE European Research Council 852178 101100859REBIRTH ZN3340
6 · The paper itself

Abstract

backgroundThere is a significant demand for intermediate-scale bioreactors in academic and industrial institutions to produce cells for various applications in drug screening and/or cell therapy. However, the application of these bioreactors in cultivating hiPSC-derived immune cells and other blood cells is noticeably lacking. To address this gap, we have developed a xeno-free and chemically defined intermediate-scale bioreactor platform, which allows for the generation of standardized human iPSC-derived hematopoietic organoids and subsequent continuous production of macrophages (iPSC-Mac).

methodsWe describe a novel method for intermediate-scale immune cell manufacturing, specifically the continuous production of functionally and phenotypically relevant macrophages that are harvested on weekly basis for multiple weeks.

resultsThe continuous production of standardized human iPSC-derived macrophages (iPSC-Mac) from 3D hematopoietic organoids also termed hemanoids, is demonstrated. The hemanoids exhibit successive stage-specific embryonic development, recapitulating embryonic hematopoiesis. iPSC-Mac were efficiently and continuously produced from three different iPSC lines and exhibited a consistent and reproducible phenotype, as well as classical functionality and the ability to adapt towards pro- and anti-inflammatory activation stages. Single-cell transcriptomic analysis revealed high macrophage purity. Additionally, we show the ability to use the produced iPSC-Mac as a model for testing immunomodulatory drugs, exemplified by dexamethasone.

conclusionsThe novel method demonstrates an easy-to-use intermediate-scale bioreactor platform that produces prime macrophages from human iPSCs. These macrophages are functionally active and require no downstream maturation steps, rendering them highly desirable for both therapeutic and non-therapeutic applications.

Indexed as

BioreactorsInduced Pluripotent Stem CellsMacrophagesOrganoidsCell Culture TechniquesCell DifferentiationHematopoiesisHumansBioreactorCell manufacturingDrug screeningHematopoiesishiPSCMacrophagesOrganoidsUp-scaling

Identifiers

PMID38886860
PMCPMC11184717

What OpenQuestion holds

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LicenceCC BY
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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.