Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Kim JW

PROVIDER: S-EPMC9130892 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Kim Jin Won JW Nam Sun Ah SA Yi Jawoon J Kim Jae Yun JY Lee Jong Young JY Park Seo-Yeon SY Sen Tugce T Choi Yoo-Mi YM Lee Jae Yeon JY Kim Hong Lim HL Kim Hyung Wook HW Park Jiwhan J Cho Dong-Woo DW Kim Yong Kyun YK

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20220324 15

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 ...[more]

PMID: 35322595

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Project description:Interface biofunctionalization strategies try to enhance and control the interaction between implants and host organism. Decellularized extracellular matrix (dECM) is widely used as a platform for bioengineering of medical implants, having shown its suitability in a variety of preclinical as well as clinical models. In this study, specifically designed, custom-made synthetic peptides were used to functionalize dECM with different cell adhesive sequences (RGD, REDV, and YIGSR). Effects on in vitro endothelial cell adhesion and in vivo endothelialization were evaluated in standardized models using decellularized ovine pulmonary heart valve cusps (dPVCs) and decellularized aortic grafts (dAoGs), respectively. Contact angle measurements and fluorescent labeling of custom-made peptides showed successful functionalization of dPVCs and dAoGs. The functionalization of dPVCs with a combination of bioactive sequences significantly increased in vitro human umbilical vein endothelial cell adhesion compared to nonfunctionalized controls. In a functional rodent aortic transplantation model, fluorescent-labeled peptides on dAoGs were persistent up to 10 days in vivo under exposure to systemic circulation. Although there was a trend toward enhanced in vivo endothelialization of functionalized grafts compared to nonfunctionalized controls, there was no statistical significance and a large biological variability in both groups. Despite failing to show a clear biological effect in the used in vivo model system, our initial findings do suggest that endothelialization onto dECM may be modulated by customized interface biofunctionalization using the presented method. Since bioactive sequences within the dECM-synthetic peptide platform are easily interchangeable and combinable, further control of host cell proliferation, function, and differentiation seems to be feasible, possibly paving the way to a new generation of multifunctional dECM scaffolds for regenerative medicine.

Dataset Information

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

Publications

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

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