November 16, 2022

Leukemia on Chip – Microphysiological Multi-Tissue System for Real-Time Monitoring of Patient-Derived Acute Lymphoblastic Leukemia

1st Call, iDoc

Short Summary

Based on recent advances in the field of microphysiological systems and microprocessing, we propose a Leukemia-on-chip concept that will lay the foundation for a novel way of mimicking blood cancer in vitro by continuously circulating acute lymphoblastic leukemia (ALL) cells in in a microfluidic system harboring relevant body tissues. The central idea and novelty lies in combining the technical capabilities of microfluidic engineering to mimic the circulating blood system with the advantages of 3D spherical microtissues that represent body tissue phenotypes and functionality, e.g. liver that enables bioactivation of prodrugs.

Goals

Our overarching goal is to push innovation in acute lymphoblastic leukemia (ALL) drug discovery by establishing a microfluidic impedance platform, which accommodates 3D microtissues and circulating cancer cells, and which will, in the long term, enable to develop treatments of many forms of ALL. At the end of the project, we aim at having a reliable in-vitro screening platform prototype and process, which then can be modified for use with other cell-circulation-based diseases.

Significance

Numerous political efforts and regulatory aspects in the EU and US indicate that improved in vitro human microtissue-based systems are needed. By increasing their predictive capacities over current cell-based systems, in-vitro systems as proposed here may also serve as an alternative to animal models and will be applicable to research and development in different fields including pharmaceutical, chemical and cosmetics industry.

Background

The importance of a personalized approach to disease is a modern achievement of medicine and has changed our approach to translational science. This project proposes to study acute lymphoblastic leukemia (ALL) in a dedicated microphysiological system. Using patient-derived xenografts (PDX) of the University Children Hospital Zürich, we have access to over 200 patient genotypes. By culturing circulating PDX ALL cells in a multi-tissue setup with liver microtissues, we will be able to investigate efficacy and toxicology of therapies simultaneously and to study bioactivation of prodrugs.

Publications

C. Sampaio da Silva, R. Limacher, C. Beyer, F. Gökçe, T. Valentin, A. Hierlemann, and V. Revol, “Electrical impedance spectroscopy platform for label-free characterization of microtissues with facing electrodes”, NanoBioTech-Montreux Conference 2022, 14-16 November 2022, Montreux, Switzerland.
Gökçe, F., Kaestli, A., Lohasz, C., de Geus, M., Kaltenbach, H.-M., Renggli, K., Bornhauser, B., Hierlemann, A., Modena, M., Microphysiological Drug-Testing Platform for Identifying Responses to Prodrug Treatment in Primary Leukemia. Adv. Healthcare Mater. 2023, 12, 2202506. https://doi.org/10.1002/adhm.202202506
F. Gökçe, P.S. Ravaynia, M. Modena, and A. Hierlemann, “What is the future of electrical impedance spectroscopy in flow cytometry?”, Biomicrofluidics 15, 061302 (2021). DOI: 10.1063/5.0073457
N. Rousset, M. de Geus, A. Kaestli, K. Renggli, A. Hierlemann. “Towards controlling the mobility of flowing cells in a hanging-drop network for microphysiological systems”, Book of Abstracts Dechema 3D Cell Culture, June 5-7, 2018, Freiburg, Germany, p. 142.