Evidence map›Paper›PMID 41601675›Full record

ArticleFrontiers in immunology2025

Robust, scalable and xeno-free protocol for differentiating human induced pluripotent stem cells into functional macrophages.

Miquel De Homdedeu, Rubén Escribá, Kenia Rodríguez-González, Sergi Querol, Jesus Fernandez-Sojo, Belén Alvarez-Palomo

Abstract read
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Targeting macrophages in liver fibrosis.Frontiers in immunology · 2026
    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

6 authors.

Miquel De HomdedeuCell Therapy Service, Banc de Sang i Teixits, Barcelona, Spain.
Rubén EscribáCell Therapy Service, Banc de Sang i Teixits, Barcelona, Spain.
Kenia Rodríguez-GonzálezCell Therapy Service, Banc de Sang i Teixits, Barcelona, Spain.
Sergi QuerolJosep Carreras Leukaemia Foundation, Barcelona, Spain.
Jesus Fernandez-SojoCell Therapy Service, Banc de Sang i Teixits, Barcelona, Spain.
Belén Alvarez-PalomoCell Therapy Service, Banc de Sang i Teixits, Barcelona, Spain.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human induced pluripotent stem cells (hiPSCs)-derived macrophages (iMacs) exhibit key macrophage phenotypic and functional properties, positioning them as promising candidates for allogenic cell immunotherapies. However, an efficient, scalable and good manufacturing practices (GMP)-compatible differentiation protocol is noticeably lacking. To meet this need, we aimed to develop a robust protocol for differentiating clinical-grade hiPSC lines into functional iMacs, designed for scalability and immediate GMP translation. We tested different media compositions, cytokine concentrations, seeding densities, culture regimens (2D vs. 3D) and coatings across key developmental stages. With the optimized protocol, we differentiated three different clinical-grade hiPSC lines towards mesoderm through embryoid body (EB) formation by agitation in 3D. Hematopoietic progenitor-producing EBs were induced to produce myeloid progenitors in agitation for 7 days. Then, myeloid progenitors were harvested and transferred to a G-Rex production platform to differentiate and further polarize into M1 or M2 iMacs. Cellular differentiation was assessed using flow cytometry panels through all developmental stages. At the final differentiated stage, iMacs were functionally characterized using the pHrodo phagocytosis assay. Pro-inflammatory cytokine secretion was analyzed by ELISA, and cell morphology was assessed by May-Grünwald Giemsa staining in Cytospin preparations. The full protocol was performed using feeder-free, scalable and either GMP or GMP- translatable reagents. This protocol enabled the production of iMacs with a mean purity of 98% viable cells, and a mean differentiation fold of 250X from a single hiPSC.

Indexed as

Cell Culture TechniquesCell DifferentiationInduced Pluripotent Stem CellsMacrophagesCell LineCells, CulturedCytokinesHumansPhagocytosisCytokinesallogenic cell therapygas-permeable rapid expansion system (G- Rex)good manufacturing practice (GMP)induced pluripotent stem cells (iPSCs)macrophage differentiationphagocytosis

Identifiers

PMID41601675
PMCPMC12833622

What Socratic 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 Socratic graph.