Kidney organoid derived from pluripotent stem cells (PSCs) have gradually become a platform to understand kidney morphogenesis, development and diseased states. Despite the abundant differentiation protocols to obtain relevant renal cell types and organoids, most of these only reach a developmental immature stage (1). We hypothesize that the limited maturation is due to absence of relevant ECM molecules that interact with signalling of the developing kidney. With this, we synthesized heparan sulphate analogue hydrogels to observe if organoid maturation will proceed upon encapsulation. Precursor molecules were successfully functionalised with both 5.2% norbornene, and 1.7 SO3 groups per disaccharide of backbone. Adsorption studies on these hydrogels show strong affinity towards growth factors relevant to the reciprocal induction signalling in the developing kidney. This demonstrates the materials’ mimicry on ECM modulated signalling of heparan sulphate. In addition, further maturation of encapsulated organoids was observed by means of immunocytochemical staining with the presence of principal and intercalated cell populations, along with reduced interstitial cells. Overall, organoid maturation may be realised with these class of materials with a more physiological model for drug discovery, disease modelling, and understanding further the developmental biology of kidney.
1 - Geuens, T., et al, Biomaterials, 275, 120976.