Fraunhofer Institute for Cell Therapy and Immunology, Branch Bioanalytics and Bioprocesses IZI-BB
Fraunhofer Institute for Cell Therapy and Immunology, Branch Bioanalytics and Bioprocesses IZI-BB

Cell Model Development

Cell-line and iPSC-based Models for Customized in vitro Applications

The development of cell lines is crucial for biomedical research, drug development, and basic research, as it ensures consistency and reproducibility of results.

We work with primary cells, primary-cell-like cells, tumor cell lines, and induced pluripotent stem cells (iPS cells) to develop customized 2D and 3D cell models for specialized applications and assays. For example, we use iPS cells to induce targeted differentiation into nerve cells and liver organoids, thereby providing physiologically relevant models for drug discovery, toxicology, and basic research.

For genetic modification, such as the integration of Genes of Interest (GOIs), we use transient transfection, stable genomic transfection via viral methods, or CRISPR/Cas. Our recombinant expression systems also enable the targeted expression of physiologically relevant and difficult-to-express genes or proteins, which can be controlled constitutively or inducibly depending on the requirements. We verify the quality and identity of our cell models using established immunological staining techniques, Western blot and qPCR-based analyses, and cell-type-specific functional assays. This allows us to reliably assess cell identity, differentiation status, and the expression of relevant markers.

Characteristics and Benefits

  • Wide range of cell models (primary cells, cell lines, iPSCs)
  • Targeted differentiation protocols for neuronal cells and liver organoids
  • Flexible culture options: serum-free, suspension, spheroids, organoids, barrier and co-culture models
  • Flexible genetic modifications: transient or stable modifications via vector transfection, lentiviral transduction, and CRISPR/Cas—with constitutive or inducible expression systems
  • Integrated analytical methods for selection and quality control (staining, qPCR, WB, cell sorting, functional assays)
  • Applicable to various fields: drug discovery, toxicology, basic cell and organoid research

 

Access our expertise to advance your research.

© Fraunhofer IZI-BB

Our Contribution to Your Project

  • Personalized consultation to help you select the right cell model for your research question
  • Management of the entire model development process—from concept to the finished, validated cell platform
  • Adaptation of differentiation and culture protocols to your infrastructure and assay requirements
  • Implementation of genetic modifications, followed by characterization and documentation

 

 

© Fraunhofer IZI-BB

  • Delivery of ready-to-use cell models, including all quality controls and protocols
  • Support with integrating the cell models into your existing workflows
  • Option for long-term collaboration on follow-up projects and optimizations

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Metabolism of Pharmaceuticals

Discover more offers and information on connected applications for this technology!

  • Drug metabolism
  • More precise screenings to accelerate your drug development

 

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PremoCell: Photonic Analytics Platform

for real-time monitoring of stem cell-based in vitro models

© Fraunhofer IPMS

As part of the PremoCell collaborative project, Fraunhofer IZI-BB is developing human liver organoids from induced pluripotent stem cells (hiPS cells).

In addition to hepatocytes, these three-dimensional models integrate other liver-associated cell types such as Kupffer cells, stellate cells, and sinusoidal endothelial cells (LSECs) to replicate key characteristics of human liver tissue and provide a human-relevant basis for the preclinical evaluation of drug candidates. A key focus is on developing a disease-relevant model for metabolic-associated steatotic liver diseases and steatohepatitis (MASLD/MASH).

At Fraunhofer IPMS, photonic sensor chips are being developed to enable time-resolved detection of selected biomarkers. By combining this sensor technology with the high-throughput 2D liver models from Fraunhofer IBMT, as well as the physiologically relevant liver organoids and disease-relevant MASLD/MASH models from Fraunhofer IZI-BB, the goal is to create a flexible platform for efficacy and toxicity studies in physiologically relevant in vitro models.

Project

iBBB: iPSC-based Blood-Brain Barrier Models

for preclinical drug Evaluation

The project involves establishing physiologically relevant cell models from induced pluripotent stem cells (iPSCs). To this end, iPSCs are cultured, characterized, and differentiated into cell types relevant to the blood-brain barrier, including endothelial cells, pericytes, and astrocytes. The cells are comprehensively tested for their identity, quality, and function—for example, through specific markers, barrier properties, and transport mechanisms. Standardized cultivation and quality control procedures, as well as cell banks, lay the foundation for the long-term, reliable use of these models in research and preclinical drug evaluation.

PhysioInk: Process-Optimized Bioinks

for real-world 3D bioprinting

In the PhysioInk collaborative project, the Fraunhofer Institutes ISC, IAP, IMWS, and IZI-BB are developing process-optimized bioinks for the 3D bioprinting of physiologically relevant tissues. The goal is to combine good printability with biological functionality in order to reproducibly produce complex tissue structures.

The Fraunhofer IAP and the Fraunhofer ISC stabilize collagen and elastin using special macromolecules. The Fraunhofer IZI-BB investigates cell-material interactions, cell compatibility, and the nutrient supply to printed tissues using optical microsensors. The bio-inks are being tested, among other things, for physiological heart tissue as well as standardized intestinal tumor models for preclinical drug development.

Project

Producing Innovative Biocatalysts with Fungal‑based Cell‑free Synthesis Platforms

»PZ-Syn: Pilzbasierte zellfreie Syntheseplattformen«

© Alexander Karich
Cystoderma lilacipes in its natural environment.

In this project, Fraunhofer IZI‑BB, BTU Cottbus–Senftenberg, and TU Dresden were developing new cell‑free synthesis platforms for the rapid production of unspecific peroxygenases (UPOs) from fungi. Non-specific peroxygenases catalyze selective oxygen transfer reactions, which also occur during the metabolism of drugs in the human liver. The similarity to liver-formed metabolites is verified using specially developed liver cell models with defined biotransformation enzymes, with the aim to develop new pharmacological test systems.

Project

Synthesis of G-Protein‑coupled Receptors - New Platforms for Targeted Drug Screening

»PZ-Syn+G: Synthese G-Protein-gekoppelter Rezeptoren«

© Fraunhofer IZI-BB

The »PZ‑Syn+G« project builds on the Fraunhofer project group »Fungal‑based cell‑free synthesis platforms« (PZ‑Syn) at the BTU Senftenberg campus and focuses on establishing a reliable production pipeline for functional G-protein‑coupled receptors (GPCRs) – a receptor family that, due to its key role in central signaling pathways, is the target of more than one‑third of approved drugs. Because of their complex structure, however, they are among the most difficult protein classes to access, creating a bottleneck for drug discovery and diagnostics.

Project

Microfluidic Bioreactors for in‑vitro Toxicity Measurements - Liver‑on‑a‑Chip

»HepatoTox: Mikrofluidische Bioreaktoren«

Microfluidic bioreactors for in-vitro toxicity measurements (Liver-on-a-Chip)
© Fraunhofer IZI-BB
Microfluidic bioreactors for in-vitro toxicity measurements (Liver-on-a-Chip)

The microphysiological system (liver‑on‑a‑chip) developed in this project for assessing the long‑term toxicity of drug compounds is intended to help replace animal testing. Real‑time concentration measurements of glucose and oxygen levels, as well as pH values, enable quality control and provide valuable time‑resolved information on hepatocyte metabolic activity when exposed to drug candidates or chemical substances.

More Info

Biotechnologically Activated Therapeutics – Tailored Platform for Precision Medicine

»NGD: Next Generation Drugs«

Fraunhofer IZI‑BB optimizes peroxygenases in cell‑free systems and develops human liver models to convert drugs such as clopidogrel and tamoxifen into highly potent, well‑tolerated metabolites. BTU and Fraunhofer IAP scale production and develop formulation and cellular testing.

Project

Methods

  • Fully equipped facility for cell culture work (S1/S2) up to bioreactor scale
  • Genetic modification of cells using viral or CRISPR-Cas-based gene transfer
  • Characterization of primary cells and cell lines, e.g., with regard to:
    • Proliferation, migration
    • Gene expression using PCR and RT-qPCR methods
    • Protein expression using microscopic and flow cytometric (immuno)detection (e.g., fluorescence staining, Western blot, FACS)
    • Enzyme activity
    • Metabolism
    • Cytotoxicity

Equipment

  • PCR (Biometra Tadvanced, Analytic Jena) and RT-qPCR (LightCycler®, Roche)
  • Flow cytometry including fluorescence-activated cell sorting (FACS Cellsorter SH800S, Sony Biotechnology)
  • Multimode plate reader ClarioStar Plus (BMG Labtech)
  • Confocal laser scanning microscope (Zeiss LSM 980 with NLO laser), incubation chamber, multiphoton excitation, fluorescence/phosphorescence lifetimes and correlations using lifetime imaging (FLIM/PLIM) and fluorescence correlation spectroscopy (FCS)
  • Fully automated fluorescence microscopes for time-lapse imaging of living cells under physiological conditions (time-lapse microscopy with incubation chambers) (CellSens; ScanR with AI)
  • TIRF microscopy (Olympus)
  • Laser tweezers / optical tweezers with laser microdissection (Palm / Zeiss)
  • Precellys Evolution Touch homogenizer (Bertin Instruments)
  • Next Generation Sequencing (NGS) (Illumina MiniSeq™)
  • HPLC (Shimadzu) and UHPLC (Ultimate 3000 nanoRSLC, Dionex)

Publications

  • Steinbrecht S, Pfeifer N, Herzog N, Katzenberger N, Schulz C, Kammerer S, Küpper J-H. HepG2-1A2 C2 and C7: Lentivirus vector-mediated stable and functional overexpression of cytochrome P450 1A2 in human hepatoblastoma cells. Toxicology Letters 319 (2020) 155–159.
  • Schulz C, Jung F, Küpper J-H. Inhibition of phase-1 biotransformation and cytostatic effects of diphenyleneiodonium on hepatoblastoma cell line HepG2 and a CYP3A4-overexpressing HepG2 cell clone. Clin Hemorheol Microcirc 79 (2021) 231-243.
  • Schulz C, Herzog N, Kubick S, Jung F, Küpper J-H. Stable Chinese Hamster Ovary Suspension Cell Lines Harboring Recombinant Human Cytochrome P450 Oxidoreductase and Human Cytochrome P450 Monooxygenases as Platform for In Vitro Biotransformation Studies. Cells 12 (2023) 2140.
  • Knauer J-F, Schulz C, Zemella A, Wüstenhagen D-A, Walter R-M, Lüpper J-H, Kubick S. Synthesis of mono Cytochrome P450 in a modified CHO‑CPR cell‑free protein production platform. Scientific Reports 14 (2024) 1271
  • Schulz C, Stegen S, Jung F, Küpper J-H. Mono-CYP CHO Model: A Recombinant Chinese Hamster Ovary Cell Platform for Investigating CYP-Specific Tamoxifen Metabolism. Int. J. Mol. Sci. 26 (2025) 3992

Patent

  • Schulz C, Küpper J-H. Testsystem aufweisend stabil CYP-transfizierte oder transduzierte Säugetierzellen. DE 10 2023 102 366.7 / WO 2024 16 08 63 A1