drei eingefärbte Organoide unter dem Mikroskop


Agnieszka Rybak-Wolf


Organoids are stem cell-derived 3D culture systems that mimic the cellular complexity and functionality of human organs, thereby bridging the gap between in vitro and in vivo research. Our platform provides services for organoids derivation and their further characterization.

The organs of the human body consist of distinct cell types that are organized in a specific manner to form a multi-layer network. Today it is possible to reconstruct organ-like tissues (organoids) in the laboratory, whereby stem cells are directed by molecular signals that drive their differentiation and are grown in culture systems that promote their three-dimensional self-organization. Organoid technologies, which are rapidly developing, allow to phenotypically copy the cellular composition and, to a certain degree, also the functionality of various human organs such as brain, thyroid, thymus, intestine, liver, pancreas, stomach, lungs, kidneys, and even early embryos. As near-physiological 3D culture systems, organoids open up new possibilities for investigating the development of healthy and diseased organs and offer great potential for translational research.

Our tools

  • Gene editing, introduction/correction of disease mutation
  • Derivation of brain organoids
  • Organoid characterization with standard molecular biology techniques:
    NanoString genomic analysis, qPCR and immunohistochemistry, microelectrode arrays (MEAs)
  • Disease modeling in vitro
  • RNAseq and single cell analysis


“The centre of my current research interest is optimization and development of brain tissue models for basic and clinical research and in particular for studying mechanisms of neurodegenerative disorders” Agnieszka Rybak-Wolf
“Here at the organoid technology platform, my motivation revolves around 2 key aspects: In general, I want to improve the translatability of organoid systems for biomedical research and real-life applications. From a more applied perspective, I aim at exploiting organoid technology to study age-related diseases” Nicolai Kastelic
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“After almost nineteen years working in different laboratories as technical assistant, I gained experience in a broad spectrum of molecular and cellular techniques. I find cell culture and in particular generation of organoids very interesting as they are exciting models for research on diseases and drug discovery “ Ruth Pareja Alcaraz

Technology & Application

Engineering brain organoid culture systems

Established in 2019, the Organoid Platform aims to support organoid-related research by providing expertise on deriving organoids from pluripotent stem cells or progenitor cells and developing methods for their subsequent characterization. The platform is part of the Berlin Institute for Medical Systems Biology (BIMSB) at the Max Delbrück Center. Currently, we are focusing on different types of brain organoids, but the range of simplified mini-organs will expand with the development of the platform.

A major goal of our platform is to further engineer brain organoid culture systems and to improve in vitro neural tissue morphogenesis. We want to implement technologies to vascularize brain organoids and to incorporate microglia (a type of non-neuronal cells in the central nervous system) into our systems in order to realize long-term maturation of three-dimensional neural tissues.

In addition, we establish published methods and develop new approaches in organoid research. A particular focus is on technologies such as single cell sequencing and RNA targeting and editing with CRISPR-Cas systems.

A collaborative effort to dissect mechanisms of disease

In close collaboration with the Pluripotent Stem Cells Platform and the Transgenics Platform at the Max Delbrück Center, we will use genome editing techniques to model and study genetic brain diseases. Examples include Leigh syndrome (a hereditary psychomotor regression in infancy) and Alzheimer's disease, where we will analyze the underlying molecular mechanisms and screen for drug candidates.

Ultimately, we would like to create a general blueprint for modern gene therapy for genetic brain diseases. To this end, we intend to combine personalized, patient-derived brain organoid models with the latest genetic tools for gene repair.




Current models

  • Cerebral and Forebrain organoids
    (Lancaster et al., 2014; PMID: 25188634,  Quian et al., 2016; PMID: 27118425)
  • ALI/enCOR organoids
    (Giandomenico et al, 2019; PMID: 30886407, Lancaster 2017; PMID: 28562594)
  • Assembloids
    (Bagley et al., 2017, PMID: 28504681)
  • Bioengineered Neuronal Organoids (BENOs)
    (Zafeiriou et al., 2020; PMID: 32728089)
  • 3D silk collagen brain tissue models
    (Chwalek et al., 2015, PMID: 26270395)




  • iPSC culture
  • NPCs culture
  • brain organoids deriviation
  • brain organoids characterization

Organoids deriviation

  • healthy lines (platform provided)
  • custom lines

Organoids preparation for scRNAseq/VISIUM

  • scRNAseq
  • spatial trancriptomics (VISIUM)

Organoids transgenesis

  • NEPA electroporation
  • lipofection
  • viral transduction

Organoids characterization

  • nanostring (standard panel)
  • nanostring (custom panel)
  • immunostaining/ISH
  • single cell RNAseq

Disease modeling

  • platform lines
  • custom lines

Gene editing/Clonal expansion