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

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Item Type:Article
Title:Tuning the 3D microenvironment of reprogrammed tubule cells enhances biomimetic modeling of polycystic kidney disease
Creators Name:Pichler, R. and Rizzo, L. and Tröndle, K. and Bühler, M. and Brucker, H. and Müller, A.L. and Grand, K. and Farè, S. and Viau, A. and Kaminski, M.M. and Kuehn, E.W. and Koch, F. and Zimmermann, S. and Koltay, P. and Lienkamp, S.S.
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:Kidney Tubules, Bioprinting, ECM-Like Biomaterials, Disease Modeling, Polycystic Kidney Disease, Direct Reprogramming
Page Range:121910
Date:December 2022
Official Publication:https://doi.org/10.1016/j.biomaterials.2022.121910
PubMed:View item in PubMed

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