What we do
About our project
Pompe disease is a lysosomal storage disorder affecting multiple tissues and particularly muscle. With a complex and heterogeneous metabolic phenotype, it is crucial to understand the molecular and physiological aspects at the cellular level. We therefore exploit the muscle-on-chip technology to focus on the myogenesis, functionality and response to drugs of human muscle fibers. Using hiPSC technology we usemyogenic progenitor cells and motor neurons to create 3D Tissue Engineered Skeletal Muscles and 3D motor neuron organoids, to study skeletal muscle and the neuromuscular junction.
We tightly collaborate with the clinical research side of our center for the optimal translation of our findings.
Our research focus
We use the technologies we developed in-house and in collaboration with commercial partners to accurately measure contractile force as a crucial and non-destructive readout of our 3D-TESMs. We focus also on the analysis of molecular and morphological features of the engineered muscles to gain deeper insights on the development of pathological phenotypes and the response to drugs and treatments.
Funds & Grants
Our work on muscle on a chip has obtained funding from Health Holland, Prinses Beatrix Spierfonds, EU-JPND, Texnet, National Growthfunds NEXTGEN and OMBION, Metakids.
Collaborations
Internal Collaborations
Dr. Yannick Taverne,
Pediatric and Congenital cardiac surgeon
Prof. Robbert Rottier and Prof. Rene Wijnen, Pediatric Surgery.
Dr. Debby van Riel, Virology.
External Collaborations
We are part of United for Metabolic Diseases (UMD), the National Consortium for clinicians and scientist on metabolic diseases.
We collaborate with Prof. Silvere van der Maarel and Dr. Jessica de Greef (LUMC) on muscle on a chip technology, with Prof. Pasterkamp(UMCU) on the neuromuscular junction, with Dr. Vittorio Saggiomo (WUR) on technology, and Dr. Massimo Mastrangeli (TUD) on technology.
We collaborate with Optics11Life and have co-developed the Cuore, a device for multichannel, real-time measurement of contractile force.
We disseminate muscle on a chip technology to multiple research groups, including those withing the skeletal muscle theme group of hDMT (https://www.hdmt.technology/about/).
We are part of the European Pompe Consortium (EPOC).
We collaborate with Bernd van Buuren to valorise our technology in a startup.
Publications
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in ’t Groen, S. L. M., de Faria, D. O. S., Iuliano, A., van den Hout, J. M. P., Douben, H., Dijkhuizen, T., Cassiman, D., Witters, P., Barba Romero, M.-Á., de Klein, A., Somers-Bolman, G. M., Saris, J. J., Hoefsloot, L. H., van der Ploeg, A. T., Bergsma, A. J., & Pijnappel, W. W. M. P. (2020). Novel GAA Variants and Mosaicism in Pompe Disease Identified by Extended Analyses of Patients with an Incomplete DNA Diagnosis. Molecular Therapy - Methods and Clinical Development, 17. https://doi.org/10.1016/j.omtm.2019.12.016
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in ’t Groen, S. L. M., Franken, M., Bock, T., Krüger, M., de Greef, J. C., & Pijnappel, W. W. M. P. (2024). A knock down strategy for rapid, generic, and versatile modelling of muscular dystrophies in 3D-tissue-engineered-skeletal muscle. Skeletal Muscle, 14(1), 3. https://doi.org/10.1186/S13395-024-00335-5/FIGURES/4
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Iuliano, A., Haalstra, M., Raghuraman, R., Bielawski, K., Bholasing, A. P., van der Wal, E., de Greef, J. C., & Pijnappel, W. W. M. P. (2023). Real-time and Multichannel Measurement of Contractility of hiPSC-Derived 3D Skeletal Muscle using Fiber Optics-Based Sensing. Advanced Materials Technologies, 8(22). https://doi.org/10.1002/ADMT.202300845
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Iuliano, A., van der Wal, E., Ruijmbeek, C. W. B., in ‘t Groen, S. L. M., Pijnappel, W. W. M. P., de Greef, J. C., & Saggiomo, V. (2020). Coupling 3D Printing and Novel Replica Molding for In House Fabrication of Skeletal Muscle Tissue Engineering Devices. Advanced Materials Technologies, 5(9), 2000344. https://doi.org/https://doi.org/10.1002/admt.202000344
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van der Wal, E., Herrero-Hernandez, P., Wan, R., Broeders, M., in ’t Groen, S. L. M., van Gestel, T. J. M., van IJcken, W. F. J., Cheung, T. H., van der Ploeg, A. T., Schaaf, G. J., & Pijnappel, W. W. M. P. (2018). Large-Scale Expansion of Human iPSC-Derived Skeletal Muscle Cells for Disease Modeling and Cell-Based Therapeutic Strategies. Stem Cell Reports, 10(6), 1975–1990. https://doi.org/10.1016/j.stemcr.2018.04.002
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van der Wal, E., Iuliano, A., in ’t Groen, S. L. M., Bholasing, A. P., Priesmann, D., Sharma, P., den Hamer, B., Saggiomo, V., Krüger, M., Pijnappel, W. W. M. P., & de Greef, J. C. (2023). Highly contractile 3D tissue engineered skeletal muscles from human iPSCs reveal similarities with primary myoblast-derived tissues. Stem Cell Reports, 18(10), 1954–1971. https://doi.org/10.1016/J.STEMCR.2023.08.014
Our team
Prof. Pim Pijnappel, PhD
Alessandro Iuliano, PhD
Federico Silvestri, MSc
Carlo Castiglione, MSc
Anjali Bholasing, BSc
Jiaxin Wu, MSc
