title: Decellularized Human Kidney Cortex Hydrogels Enhance Kidney Microvascular Endothelial Cell Maturation and Quiescence.
abstract: The kidney peritubular microvasculature is highly susceptible to injury from drugs and toxins, often resulting in acute kidney injury and progressive chronic kidney disease. Little is known about the process of injury and regeneration of human kidney microvasculature, resulting from the lack of appropriate kidney microvascular models that can incorporate the proper cells, extracellular matrices (ECMs), and architectures needed to understand the response and contribution of individual vascular components in these processes. In this study, we present methods to recreate the human kidney ECM (kECM) microenvironment by fabricating kECM hydrogels derived from decellularized human kidney cortex. The majority of native matrix proteins, such as collagen-IV, laminin, and heparan sulfate proteoglycan, and their isoforms were preserved in similar proportions as found in normal kidneys. Human kidney peritubular microvascular endothelial cells (HKMECs) became more quiescent when cultured on this kECM gel compared with culture on collagen-I-assessed using phenotypic, genotypic, and functional assays; whereas human umbilical vein endothelial cells became stimulated on kECM gels. We demonstrate for the first time that human kidney cortex can form a hydrogel suitable for use in flow-directed microphysiological systems. Our findings strongly suggest that selecting the proper ECM is a critical consideration in the development of vascularized organs on a chip and carries important implications for tissue engineering of all vascularized organs.
authors.affiliation: 1 Department of Bioengineering, University of Washington , Seattle, Washington.|2 Department of Medicine, University of Washington , Seattle, Washington.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Nagao
authors.affiliation: 1 Department of Bioengineering, University of Washington , Seattle, Washington.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: 1 Department of Bioengineering, University of Washington , Seattle, Washington.
authors.forename: Ping
authors.initials: P
authors.lastname: Luo
authors.affiliation: 1 Department of Bioengineering, University of Washington , Seattle, Washington.
authors.forename: Jun
authors.initials: J
authors.lastname: Xue
authors.affiliation: 3 Bloodworks Northwest Research Institute , Seattle, Washington.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1 Department of Bioengineering, University of Washington , Seattle, Washington.
authors.forename: Surya
authors.initials: S
authors.lastname: Kotha
authors.affiliation: 1 Department of Bioengineering, University of Washington , Seattle, Washington.|4 Department of Anatomy, Key Lab of Biomechanics, Third Military Medical University , Chongqing, China .
authors.forename: Wen
authors.initials: W
authors.lastname: Zeng
authors.affiliation: 3 Bloodworks Northwest Research Institute , Seattle, Washington.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Fu
authors.affiliation: 2 Department of Medicine, University of Washington , Seattle, Washington.|5 Kidney Research Institute, University of Washington , Seattle, Washington.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Himmelfarb
authors.affiliation: 1 Department of Bioengineering, University of Washington , Seattle, Washington.|5 Kidney Research Institute, University of Washington , Seattle, Washington.|6 Institute for Stem Cell and Regenerative Medicine, University of Washington , Seattle, Washington.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D060833:Cellular Microenvironment; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D007672:Kidney Cortex / Q000737:chemistry*
chemical_list: D020100:Hydrogels