Translational research : the journal of laboratory and clinical medicine
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The kidney is a vital organ that regulates the bodily fluid and electrolyte homeostasis via tailored urinary excretion. Kidney injuries that cause severe or progressive chronic kidney disease have driven the growing population of patients with end-stage kidney disease, leading to substantial patient morbidity and mortality. This irreversible kidney damage has also created a huge socioeconomical burden on the healthcare system, highlighting the need for novel translational research models for progressive kidney diseases. ⋯ By applying gene editing technology, organoid building blocks may be modified to minimize the process of immune rejection in kidney transplant recipients. In the foreseeable future, the universal kidney organoids derived from HLA-edited/deleted induced pluripotent stem cell (iPSC) lines may enable the supply of bioengineered organotypic kidney structures that are immune-compatible for the majority of the world population. Here, we summarize recent advances in kidney organoid research coupled with novel technologies such as organoids-on-chip and biofabrication of 3D kidney tissues providing convenient platforms for high-throughput drug screening, disease modelling, and therapeutic applications.
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Patient-derived tumor organoids (PDTOs) have emerged as exceptional pre-clinical models as they preserved, in most of the cases, the mutational landscape and tumor-clonal heterogeneity of the primary tumors. Despite being extensively used in disease modelling as well as in precision medicine for drug testing and discovery, they still have some limitations. The main limitation is that during their establishment they lose all components of the tumor microenvironment (TME) which are known modulators of tumor response to therapeutic treatment as well as disease progression. In this review we address the effects of different players of the TME such as immune cells, fibroblasts, endothelial cells and the extracellular matrix composition on tumor behavior and response to treatment as well as the different culture and co-culture strategies that could improve PDTOs value as pre-clinical models leading to the development of next generation PDTOs.