Abstract: Adult stem cell-derived renal tubuloids are three-dimensional (3D) structures that replicate the epithelial cellular composition and spatial organization characteristic of kidney tubules. Likewise other tissue-derived organoids, tubuloids have generally been cultured using commercially available extracellular matrix (ECM) derived from mouse sarcomas. However, despite its widespread use, this tumor-derived ECM comes with critical limitations, including high costs, insufficient tissue specificity and safety concerns, which hinder its broader application in kidney research. To address these limitations, we developed biocompatible kidney mimicking hydrogel enriched with various components beneficial for tubuloid development. Our hydrogel provided an optimal microstructure and mechanical properties to support tubuloid culture. Moreover, tubuloids cultured in our hydrogel exhibited comparable or higher expression levels of kidney-specific genes and proteins compared to those grown in conventional matrix. We then demonstrated that our hydrogel enables the long-term cultivation of tubuloids and confirmed that these tubuloids showed robust trans-epithelial transport functions of kidney proximal tubule cells. In conclusion, our tubuloid culture platform holds great potential for broad applications including the evaluating drug toxicity, modeling kidney-related diseases, and understanding critical mechanisms of proximal tubule differentiation and function.
Funding Source: This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government, the Ministry of Science and ICT(MSIT) (RS-2021-NR059722)
