Tuning the 3D microenvironment of reprogrammed tubule cells enhances biomimetic modeling of polycystic kidney disease

Roman Pichler; Ludovica Rizzo; Kevin Tröndle; Michaela Bühler; Hanna Brucker; Anna-Lena Müller; Kelli Grand; Silvia Farè; Amandine Viau; Michael M Kaminski; E Wolfgang Kuehn; Fritz Koch; Stefan Zimmermann; Peter Koltay; Soeren S Lienkamp

doi:10.1016/j.biomaterials.2022.121910

Tuning the 3D microenvironment of reprogrammed tubule cells enhances biomimetic modeling of polycystic kidney disease

Biomaterials. 2022 Dec:291:121910. doi: 10.1016/j.biomaterials.2022.121910. Epub 2022 Nov 8.

Authors

Affiliations

¹ Department of Medicine IV, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
² Institute of Anatomy, University of Zurich, Zurich, Switzerland; Molecular and Translational Biomedicine PhD Program, Life Science Zurich Graduate School, Zurich, Switzerland.
³ Laboratory for MEMS Applications, IMTEK - Department of Microsystems Engineering, University of Freiburg, Freiburg, Germany.
⁴ Institute of Anatomy, University of Zurich, Zurich, Switzerland.
⁵ Department of Chemistry, Materials and Chemical Engineering "G. Natta", Politecnico di Milano, Milan, Italy.
⁶ Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany; Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany; Berlin Institute of Health, Berlin, Germany.
⁷ Department of Medicine IV, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Institute of Anatomy, University of Zurich, Zurich, Switzerland. Electronic address: soeren.lienkamp@uzh.ch.

PMID: 36403325
DOI: 10.1016/j.biomaterials.2022.121910

Abstract

Renal tubular cells frequently lose differentiation markers and physiological properties when propagated in conventional cell culture conditions. Embedding cells in 3D microenvironments or controlling their 3D assembly by bioprinting can enhance their physiological properties, which is beneficial for modeling diseases in vitro. A potential cellular source for modeling renal tubular physiology and kidney diseases in vitro are directly reprogrammed induced renal tubular epithelial cells (iRECs). iRECs were cultured in various biomaterials and as bioprinted tubular structures. They showed high compatibility with the embedding substrates and dispensing methods. The morphology of multicellular aggregates was substantially influenced by the 3D microenvironment. Transcriptomic analyses revealed signatures of differentially expressed genes specific to each of the selected biomaterials. Using a new cellular model for autosomal-dominant polycystic kidney disease, Pkd1^-/- iRECs showed disrupted morphology in bioprinted tubules and a marked upregulation of the Aldehyde dehydrogenase 1a1 (Aldh1a1). In conclusion, 3D microenvironments strongly influence the morphology and expression profiles of iRECs, help to unmask disease phenotypes, and can be adapted to experimental demands. Combining a direct reprogramming approach with appropriate biomaterials will facilitate construction of biomimetic kidney tubules and disease models at the microscale.

Keywords: Bioprinting; Direct reprogramming; Disease modeling; ECM-Like biomaterials; Kidney tubules; Polycystic kidney disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biocompatible Materials
Biomimetics*
Epithelial Cells
Humans
Kidney
Polycystic Kidney Diseases*

Substances

Biocompatible Materials