Fraunhofer Institute for Toxicology and Experimental Medicine
Fraunhofer Institute for Toxicology and Experimental Medicine

Application example: “Stem Cell Technologies”

Human immune cells (Macrophages) derived from iPSCs

© Fraunhofer ITEM, Ralf Mohr

The focus is on macrophages – immune cells that play a central role in tissue function and immune system balance in organs such as the lungs, heart, and brain. Depending on the stimulus, such as pathogens or toxic substances, they respond in either an anti-inflammatory or pro-inflammatory manner and help coordinate the immune response. When this regulation is disrupted, chronic inflammation, fibrosis, or cancer can develop.

Use of differentiated immune cells in testing systems

  • iMacroMAT: iPSC-derived macrophages for customized pyrogen testing
  • nanoparticle toxicity and immunomodulatory effects (mode of action, validation)
  • material and surface (immuno)compatibility
  • testing of immunomodulatory substances (e.g., PFAS, cytokine inhibitors, immunomodulators)
  • sensitization studies for substances with inhalation exposure
  • development of immunocompetent organ systems and organoids with integrated macrophages
  • infection models using pathogenic microorganisms or viral components
  • inflammation models for analyzing cytokine release and immune responses
  • pharmacological studies on immune activation, suppression, or drug penetration
  • long-term cultures for investigating chronic immune reactions
  • comparative studies between macrophage subtypes (e.g., M1/M2 polarization, including comparisons to primary cells such as PBMC-derived macrophages)
  • cross-talk analyses in multicellular organoids and MPS platforms
Reaktor iPSC
© Fraunhofer ITEM

From precursors to functional immune cells

Scalable production and co-development of human immune cell models

  • hematopoietic precursor cells with broad differentiation potential into various immune cell subtypes
  • macrophages – including pro- and anti-inflammatory subtypes, tissue-specific, and disease-associated macrophages
  • scalable production and custom development of immune cell types for research, screening, and toxicity testing
  • NK cells and other functional immune cell models for integration into 2D cultures, organoids, and MPS platforms

Scalability – Automation – Continuity

Efficient development and production of human cell models

  1. Media and reagents: evaluation of new culture media, cytokines, and materials for use in iPSC-based immune cell production
  2. Scalable production: testing and optimization of existing partner protocols (PoC) for large-scale manufacturing processes
  3. Automation: advancement toward standardized, automated workflows for reproducible results
  4. Continuous production: collaborative development of new manufacturing methods and provision of ready-to-use cells for research and applications

"iMacroMAT"

iPSC-derived macrophages for customization of Pyrogen Testing: Scalable and adaptable production of macrophages for testing parenteral substances in the Monocyte Activation Test to regulatory compliance.

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Fraunhofer Attract project »IMMUNITY – Designer immune cells«

In the project novel immune cell platforms for health research” induced pluripotent stem cells (iPSCs) are investigated.

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Stem cell technologies: Relevant Publications

Basílio-Queirós D, Rivière I, van der Stegen SJC, Lachmann N. iPSC-derived T cells and macrophages: Manufacturing and next-generation application approaches. Adv Drug Deliv Rev. 2025 Oct 13;227:115713. doi: 10.1016/j.addr.2025.115713. Epub ahead of print. PMID: 41093244.

Saleh F, Lachmann N, “Harnessing Intermediate-Scale Bioreactors for Next-Generation Macrophage Production and Application” Nature Protocols, 2025, accepted

Durán V, Nikolouli E, Chatterjee S, Costa B, Pavlou A, Ziegler A, Becker J, Baumann K, Bruhn M, Haake K, Hashtchin AR, Gensch I, Korte A, Behrens YL, Zhang SY, Casanova JL, Bär C, Lachmann N, Thum T, Kalinke U. Type I IFNs Decrease SARS-CoV-2 Replication in Human Cardiomyocytes and Increase Cytokine Production in Macrophages. J Clin Immunol. 2025 Oct 21;45(1):149. doi: 10.1007/s10875-025-01943-6. PMID: 41117873; PMCID: PMC12540622.

Basílio-Queirós D, Lachmann N. In vivo macrophage engineering for renal cancer therapy. Nat Cancer. 2025 May;6(5):743-745. doi: 10.1038/s43018-025-00912-7. PMID: 40301654.

Ackermann M, Saleh F, Abdin SM, Rafiei Hashtchin A, Gensch I, Golgath J, Carvalho Oliveira M, Nguyen AHH, Gaedcke S, Fenske A, Jang MS, Jirmo AC, Abeln M, Hansen G, Lachmann N. Standardized generation of human iPSC-derived hematopoietic organoids and macrophages utilizing a benchtop bioreactor platform under fully defined conditions. Stem Cell Res Ther. 2024 Jun 18;15(1):171. doi: 10.1186/s13287-024-03785-2. PMID: 38886860; PMCID: PMC11184717.

Rodriguez Gonzalez C, Basílio-Queirós D, Neehus AL, Merkert S, Tschritter D, Ünal S, Hegermann J, Mörgelin M, Bustamante J, Nietert MM, Martin U, Tümmler B, Munder A, Lachmann N. Human CFTR deficient iPSC-macrophages reveal impaired functional and transcriptomic response upon Pseudomonas aeruginosa infection. Front Immunol. 2024 Nov 13;15:1397886. doi: 10.3389/fimmu.2024.1397886. PMID: 39606224; PMCID: PMC11601075.

Paasch D, Lachmann N. CAR macrophages tuning the immune symphony of anti-cancer therapies. Cell Stem Cell. 2024 Jun 6;31(6):791-793. doi: 10.1016/j.stem.2024.05.006. PMID: 38848684.

Abdin SM, Mansel F, Hashtchin AR, Ackermann M, Hansen G, Becker B, Kick B, Pham N, Dietz H, Schaniel C, Martin U, Spreitzer I, Lachmann N. Sensor macrophages derived from human induced pluripotent stem cells to assess pyrogenic contaminations in parenteral drugs. Biofabrication. 2024 May 17;16(3). doi: 10.1088/1758-5090/ad4744. PMID: 38701770.

Abdin SM, Paasch D, Kloos A, Oliveira MC, Jang MS, Ackermann M, Stamopoulou A, Mroch PJ, Falk CS, von Kaisenberg CS, Schambach A, Heuser M, Moritz T, Hansen G, Morgan M, Lachmann N. Scalable generation of functional human iPSC-derived CAR-macrophages that efficiently eradicate CD19-positive leukemia. J Immunother Cancer. 2023 Dec 22;11(12):e007705. doi: 10.1136/jitc-2023-007705. PMID: 38135346; PMCID: PMC10749073.

Malainou C, Abdin SM, Lachmann N, Matt U, Herold S. Alveolar macrophages in tissue homeostasis, inflammation, and infection: evolving concepts of therapeutic targeting. J Clin Invest. 2023 Oct 2;133(19):e170501. doi: 10.1172/JCI170501. PMID: 37781922; PMCID: PMC10541196.

Ackermann M, Rafiei Hashtchin A, Manstein F, Carvalho Oliveira M, Kempf H, Zweigerdt R, Lachmann N. Continuous human iPSC-macrophage mass production by suspension culture in stirred tank bioreactors. Nat Protoc. 2022 Feb;17(2):513-539. doi: 10.1038/s41596-021-00654-7. Epub 2022 Jan 17. PMID: 35039668; PMCID: PMC7612500.