Differentiated kidney tubular cell-derived extracellular vesicles enhance maturation of tubuloids

Autor: Soares Lindoso, Rafaël, Yousef Yengej, Fjodor A., Völlmy, Franziska, Altelaar, Maarten, Juncosa, Estela Mancheno, Tsikari, Theano, Ammerlaan, Carola M.E., van Balkom, B, Rookmaaker, M.B., Verhaar, M.C., Masereeuw, Rosalinde, Afd Pharmacology, Afd Biomol.Mass Spect. and Proteomics, Pharmacology, Biomolecular Mass Spectrometry and Proteomics
Přispěvatelé: Afd Pharmacology, Afd Biomol.Mass Spect. and Proteomics, Pharmacology, Biomolecular Mass Spectrometry and Proteomics
Rok vydání: 2022
Předmět:
Zdroj: Journal of Nanobiotechnology, 20(1), 1. BioMed Central
ISSN: 1477-3155
DOI: 10.1101/2022.02.08.479621
Popis: Advanced kidney in vitro models such as organoids or tubuloids still lack the intrinsic expression of various transport proteins needed for active secretory function. Extracellular vesicles (EVs), cell-derived structures that constitute the organ’s microenvironment, are known to regulate various cellular processes, including kidney development and regeneration across the nephron. In this study, we propose a new application of renal tubular epithelial cell EVs as modulators for tubuloid functional maturation by increasing the levels of various differentiation markers such as organic anion transport 1 (OAT1), a protein involved in endogenous waste excretion. First, we show that EVs from engineered proximal tubule cells increased the expression of several transcription factors and epithelial transporters in tubuloids that resulted in improved cellular transport capacity. Next, a more in-depth proteomic data analysis demonstrated that EVs can trigger various biological pathways, including mesenchymal-to-epithelial transition, which is crucial in the tubular epithelial maturation process. Moreover, we demonstrated that EV-treated tubuloid-derived cells in a 3D tubular conformation as part of a bioartificial kidney can generate a tight polarized epithelial monolayer with formation of dense cilia structures. In conclusion, EVs from renal tubular epithelial cells can phenotypically improve tubuloid maturation, thereby enhancing their potential as preclinical models and functional units in regenerative therapies.
Databáze: OpenAIRE
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