2024 | Elena Garreta, Daniel Moya-Rull, Andrés Marco, Gaia Amato, Asier Ullate-Agote, Carolina Tarantino, Maria Gallo, David Esporrín-Ubierto, Alberto Centeno, Amaia Vilas-Zornoza, Rafael Mestre, María Kalil, Izar GorroñoGoitia, Ane Miren Zaldúa, Samuel Sanchez, Laura Izquierdo Reyes, María Eugenia Fernández-Santos, Felipe Prosper, and Nuria Montserrat
Natural hydrogels derived from decellularized kidney extracellular matrix (dECM) support kidney organoid generation and promote in vitro angiogenesis. This study demonstrates that using porcine and human kidney dECM hydrogels in combination with human pluripotent stem cell (hPSC)-derived renal progenitor cells enables the differentiation of kidney organoids with renal features and endogenous vascular components. The hydrogels facilitate the self-organization of hPSC-derived renal progenitor cells into complex multicellular structures, including vascular components. A new method for generating kidney-endothelial assembloids with vascular-like structures is defined through the assembly of hPSC-derived endothelial-like organoids with kidney organoids in 3D. The study shows that natural-derived hydrogels enhance kidney organoid differentiation and vascularization, as evidenced by RNA sequencing, immunofluorescence, and image analysis. The hydrogels also support the formation of vascular-like structures in kidney organoids, as demonstrated by their transplantation in the chick chorioallantoic membrane (CAM). The results indicate that natural-derived hydrogels can be used to control the differentiation and vascularization of kidney organoids, offering new insights into kidney organoid morphogenesis and ECM interactions. The study highlights the potential of these hydrogels for applications in personalized medicine and disease modeling, particularly in understanding vascular dysfunction in diseases like diabetic nephropathy. The findings suggest that optimizing the use of natural hydrogels could lead to more effective and robust methods for generating functional kidney organoids for transplantation and disease research.Natural hydrogels derived from decellularized kidney extracellular matrix (dECM) support kidney organoid generation and promote in vitro angiogenesis. This study demonstrates that using porcine and human kidney dECM hydrogels in combination with human pluripotent stem cell (hPSC)-derived renal progenitor cells enables the differentiation of kidney organoids with renal features and endogenous vascular components. The hydrogels facilitate the self-organization of hPSC-derived renal progenitor cells into complex multicellular structures, including vascular components. A new method for generating kidney-endothelial assembloids with vascular-like structures is defined through the assembly of hPSC-derived endothelial-like organoids with kidney organoids in 3D. The study shows that natural-derived hydrogels enhance kidney organoid differentiation and vascularization, as evidenced by RNA sequencing, immunofluorescence, and image analysis. The hydrogels also support the formation of vascular-like structures in kidney organoids, as demonstrated by their transplantation in the chick chorioallantoic membrane (CAM). The results indicate that natural-derived hydrogels can be used to control the differentiation and vascularization of kidney organoids, offering new insights into kidney organoid morphogenesis and ECM interactions. The study highlights the potential of these hydrogels for applications in personalized medicine and disease modeling, particularly in understanding vascular dysfunction in diseases like diabetic nephropathy. The findings suggest that optimizing the use of natural hydrogels could lead to more effective and robust methods for generating functional kidney organoids for transplantation and disease research.