News
A genetically inducible endothelial niche enables vascularization of human kidney organoids with multilineage maturation and emergence of renin expressing cells (Neil Hukriede, Univ of Pitt)
Jul 17, 2024
Neil Hukriede (Univ of Pittsburgh) of the AKI Therapeutics group just published a paper in Kidney International - with many other RBK authors! - that describes the successful use of a genetically inducible system to enhance vascularization and cell maturation in human kidney organoids. (See graphical abstract below.)
A genetically inducible endothelial niche enables vascularization of human kidney organoids with multilineage maturation and emergence of renin expressing cells
Authors: Maggiore, Joseph C.; LeGraw, Ryan; Przepiorski, Aneta; Velazquez, Jeremy; Chaney, Christopher; Vanichapol, Thitinee; Streeter, Evan; Almuallim, Zainab; Oda, Akira; Chiba, Takuto; Silva-Barbosa, Anne; Franks, Jonathan; Hislop, Joshua; Hill, Alex; Wu, Haojia; Pfister, Katherine; Howden, Sara E.; Watkins, Simon C.; Little, Melissa H.; Humphreys, Benjamin D.; Kiani, Samira; Watson, Alan; Stolz, Donna B.; Davidson, Alan J.; Carroll, Tom; Cleaver, Ondine; Sims-Lucas, Sunder; Ebrahimkhani, Mo R. and Hukriede, Neil A.
Journal: Kidney International
DOI: https://doi.org/10.1016/j.kint.2024.05.026
Summary:
Vascularization plays a critical role in organ maturation and cell-type development. Drug discovery, organ mimicry, and ultimately transplantation hinge on achieving robust vascularization of in vitro engineered organs. Here, focusing on human kidney organoids, we overcame this hurdle by combining a human induced pluripotent stem cell (iPSC) line containing an inducible ETS translocation variant 2 (ETV2) (a transcription factor playing a role in endothelial cell development) that directs endothelial differentiation in vitro, with a non-transgenic iPSC line in suspension organoid culture. The resulting human kidney organoids show extensive endothelialization with a cellular identity most closely related to human kidney endothelia. Endothelialized kidney organoids also show increased maturation of nephron structures, an associated fenestrated endothelium with de novo formation of glomerular and venous subtypes, and the emergence of drug-responsive renin expressing cells. The creation of an engineered vascular niche capable of improving kidney organoid maturation and cell type complexity is a significant step forward in the path to clinical translation. Thus, incorporation of an engineered endothelial niche into a previously published kidney organoid protocol allowed the orthogonal differentiation of endothelial and parenchymal cell types, demonstrating the potential for applicability to other basic and translational organoid studies.
