Translational research : the journal of laboratory and clinical medicine
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The ability to generate human retinas in vitro from pluripotent stem cells opened unprecedented opportunities for basic science and for the development of therapeutic approaches for retinal degenerative diseases. Retinal organoid models not only mimic the histoarchitecture and cellular composition of the native retina, but they can achieve a remarkable level of maturation that allows them to respond to light stimulation. However, studies evaluating the nature, magnitude, and properties of light-evoked responsivity from each cell type, in each retinal organoid layer, have been sparse. In this review we discuss the current understanding of retinal organoid function, the technologies used for functional assessment in human retinal organoids, and the challenges and opportunities that lie ahead.
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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.