Decellularized porcine kidney-incorporated hydrogels for cell-laden bioprinting of renal cell carcinoma model

Abstract

More than 90% of kidney cancers are attributed to renal cell carcinoma (RCC), which is however highly resistant to traditional chemotherapy. The challenges met in treating RCC signify an imperative to accelerate the development of new and effective drugs. Preclinical testing has served as a foundation for evaluating potential effectiveness of new drugs, but this endeavor is deeply restricted by the current generation of in vitro two-dimensional culture models, which cannot accurately mimic the tumor microenvironment (TME). Therefore, new in vitro three-dimensional (3D) cell culture models that can better mimic the components and architecture of TME have been developed for preclinical testing, but only a few existing 3D cell culture models can simulate the TME of RCC, representing a limitative obstacle impeding the development of novel drugs for RCC. In this study, we prepared a bioink by mixing porcine kidney decellularized extracellular matrix (dECM) powders with gelatin methacryloyl (GelMA) to bioprint an in vitro 3D cell culture model for RCC. We found that GelMA stability, mechanical properties, and printability were all significantly improved following the addition of the dECM powder. Moreover, cell cultures using ACHN cells suggested that kidney dECM powders significantly improved the cellular proliferation and metastasis via upregulation of markers related to epithelial– mesenchymal transition, along with activation of several cancer progression-related signaling pathways. More importantly, ACHN cells also demonstrated higher resistance to sunitinib under the stimulation of kidney dECM, indicating that GelMA-kidney dECM hydrogels may be an appropriate preclinical model to be used for building an in vitro RCC platform for drug screening and development.