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Prof. Dr. Rüdiger Rudolf

3D Cell Models for Fundamental and Applied Research

Based on 20 years of research on mouse skeletal muscle, neuromuscular junctions, their innervation by sympathetic neurones, and mechanisms of postsynaptic protein trafficking, we are now focusing on 3D-cell models for fundamental and applied pharmaceutical research, often in cooperation with academic and industrial partners. These cell-based models are mainly for neuronal or cancer research and range from spheroids over chip-based assays up to complex cocultures and organoids. Technological foci are on development of adequate cell culturing techniques, including 3D bioprinting, but also optical tissue clearing protocols, 3D and 4D confocal and light sheet microscopy, and AI-based automated image analysis. In the context of neurosciences, we have been concentrating on the establishment of models for the neuromuscular junction (NMJ).

Central research topics:

  • Identifying modes for producing robust three-dimensional neuromuscular in vitro models containing motor neurons, Schwann cells, and muscle fibers.
  • Identifying the role of cellular communication for maturation and functional properties of the contributing cell types.
Motoneurons, skeletal muscle fibers, and Schwann cells form synapses, termed neuromuscular junctions (NMJs). These control voluntary body movement and are affected in numerous neuromuscular diseases. Therefore, a variety of NMJ in vitro models have been explored to enable mechanistic and pharmacological studies. We are exploring modes of creating models of NMJ. So far, we presented robust protocols for derivation of Schwann cells from human induced pluripotent stem cells (hiPSC) and their coculture with hiPSC-derived motoneurons and C2C12 muscle cells. Inclusion of Schwann cells in coculture experiments with hiPSC-derived motoneurons and C2C12 myoblasts enhanced myotube growth and affected size and number of acetylcholine receptor plaques on myotubes. Currently, we are working on replacing C2C12 cells by iPSC-derived muscle fibres in the coculture model and to use 3D-bioprinting to create three-dimensional NMJ organoid models. In addition, the group is involved in a number of cooperations with academic and industrial partners for setting up of further 3D-cell models for fundamental and applied research.

Research projects

MWK: Collaborative research training group "Personalized Medicine and Organoid Pharmaceutical Test Models: Advanced Materials, Analytics, and Computing (Perpharmance)". Project duration: 03/2023 – 02/2026, co-speaker

BMBF: FH-Impuls "M2Aind". Project duration: 01/2023 – 12/2024

  • Subproject: Drugs-Data.

BMBF: Synthesis For Synthesis (Syn4Syn): Modelling 3D-Organoids for the Pharmaceutical Drug Screening by Combining Experiment, AI, and Biophysics. Project duration: 01/2022 – 12/2023

DFG: Integrative Analysis of Organoids Enables Mechanistic Studies in Pharmaceutical Research: Development, Volatilomics, Single Cell Metabolite/Lipid Fingerprinting, and Function. Duration: 2022 – 2027

BMBF: FH-Impuls "M2Aind". Project duration: 01/2021 – 12/2022

  • Subproject: Drugs4Future.

Carl Zeiss foundation: DigiFIT. Project duration: 02/2019 – 01/2022

BMBF: FH-Impuls "M2Aind". Project duration: 01/2017 – 12/2020

  • Subproject: M2OGA.

BMBF: FH-Impuls “Multimodal Analytics and Intelligent Sensorics for the Health Industries”. Duration: 2017 – 2025

BMBF: Forschungscampus Mannheim Molecular Intervention Environment: Molekulare Bioanalytik und Theranostika-Entwicklung. Duration: 2015 – 2025

Legend: DFG = German Research Foundation, BMBF = Federal Ministry of Education and Research, MWK = Ministry of Science, Research and the Arts

Selected publications

  1. Development and In Vitro Differentiation of Schwann Cells.
    Hörner SJ, Couturier N, Gueiber DC, Hafner M, Rudolf R. Cells. 2022. 11(23):3753.
  2. hiPSC-Derived Schwann Cells Influence Myogenic Differentiation in Neuromuscular Cocultures
    Hörner SJ, Couturier N, Bruch R, Koch P, Hafner M, Rudolf R. Cells. 2021. 10:3292
  3. Sweet Taste Is Complex: Signaling Cascades and Circuits Involved in Sweet Sensation.
    von Molitor E, Riedel K, Krohn M, Hafner M, Rudolf R, Cesetti T. Front Hum Neurosci. 2021. 15: 667709
  4. Regulatory Function of Sympathetic Innervation on the Endo/Lysosomal Trafficking of Acetylcholine Receptor.
    Straka T, Schröder C, Roos A, Kollipara L, Sickmann A, Williams MPI, Hafner M, Khan MM, Rudolf R. Front Physiol. 2021. 12:626707
  5. Effects of ASC Application on Endplate Regeneration Upon Glycerol-Induced Muscle Damage.
    Rigon M, Hörner SJ, Straka T, Bieback K, Gretz N, Hafner  M, Rudolf R. Front. Mol. Neurosci. 2020. 13:107
  6. Analysis of calcium signaling in live human Tongue cell 3D-Cultures upon tastant perfusion.
    von Molitor E, Nürnberg E, Ertongur-Fauth T, Scholz P, Riedel K, Hafner M, Rudolf R, Cesetti T. Cell Calcium 2020, 87, 102164
  7. Motor Endplate - Anatomical, Functional, and Molecular Concepts in the Historical Perspective.
    Rudolf R, Khan MM, Witzemann V. Cells. 2019. 8:387
  8. A Novel Optical Tissue Clearing Protocol for Mouse Skeletal Muscle to Visualize Endplates in Their Tissue Context.
    Williams MPI, Rigon M, Straka T, Hörner SJ, Thiel M, Gretz N, Hafner M, Reischl M, Rudolf R. Front. Cell. Neurosci. 2019. 13:49
  9. Postnatal Development and Distribution of Sympathetic Innervation in Mouse Skeletal Muscle.
    Straka T, Vita V, Prokshi K, Hörner SJ, Khan MM, Pirazzini M, Williams MPI, Hafner M, Zaglia T, Rudolf R. Int. J. Mol. Sci. 2018. 19:1935
  10. Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease.
    Khan MM, Lustrino D, Silveira WA, Wild F, Straka T, Issop Y, O’Connor E, Cox D, Reischl M, Marquardt T, Labeit D, Labeit S, Benoit E, Molgó J, Lochmüller H, Witzemann V, Kettelhut IC, Navegantes LCC, Pozzan T, Rudolf R. Proc. Natl. Acad. Sci. 2016. 113:746–750

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