Kidney Decellularized Extracellular Matrix Enhanced the Vascularization and Maturation of Human Kidney Organoids

• Published in: Advanced science 2022-05, Vol.9 (15), p.e2103526-n/a
• Main Authors: Kim, Jin Won, Nam, Sun Ah, Yi, Jawoon, Kim, Jae Yun, Lee, Jong Young, Park, Seo‐Yeon, Sen, Tugce, Choi, Yoo‐mi, Lee, Jae Yeon, Kim, Hong Lim, Kim, Hyung Wook, Park, Jiwhan, Cho, Dong‐Woo, Kim, Yong Kyun
• Format: Article
• Language: English
• Subjects: Animals; Cell growth; Chromatography; Collagen; Decellularized Extracellular Matrix; Endothelial Cells; Extracellular matrix; Glycoproteins; Growth factors; Heparan sulfate; Humans; Hydrogels; Kidney; Kidney diseases; Mass spectrometry; Mice; organoid; Organoids; Pluripotent Stem Cells; Proteins; Protocol; Rheology; Scanning electron microscopy; Scientific imaging; vascularization
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202103526

Kidney organoids derived from human pluripotent stem cells (hPSCs) have extensive potential for disease modelling and regenerative medicine. However, the limited vascularization and immaturity of kidney organoids have been still remained to overcome. Extracellular matrix (ECM) can provide mechanical support and a biochemical microenvironment for cell growth and differentiation. Here in vitro methods using a kidney decellularized extracellular matrix (dECM) hydrogel to culture hPSC‐derived kidney organoids, which have extensive vascular network and their own endothelial cells, are reported. Single‐cell transcriptomics reveal that the vascularized kidney organoids cultured using the kidney dECM have more mature patterns of glomerular development and higher similarity to human kidney than those cultured without the kidney dECM. Differentiation of α‐galactosidase A (GLA)‐knock‐out hPSCs generated using CRISPR/Cas9 into kidney organoids by the culture method using kidney dECM efficiently recapitulate Fabry nephropathy with vasculopathy. Transplantation of kidney organoids with kidney dECM into kidney of mouse accelerates the recruitment of endothelial cells from the host mouse kidney and maintains vascular integrity with the more organized slit diaphragm‐like structures than those without kidney dECM. The kidney dECM methodology for inducing extensive vascularization and maturation of kidney organoids can be applied to studies for kidney development, disease modeling, and regenerative medicine. The limited vascularization and immaturity of kidney organoids are still to be overcome. Here in vitro methods using a kidney dECM hydrogel to culture hPSC‐derived kidney organoids, which have extensive vascular network with their own endothelial cells and matured nephron‐like structures, are reported. This methodology can be applied to studies for kidney development, disease modeling, and regenerative medicine.