title: A human in vitro model that mimics the renal proximal tubule.
abstract: Human in vitro-manufactured tissue and organ models can serve as powerful enabling tools for the exploration of fundamental questions regarding cell, matrix, and developmental biology in addition to the study of drug delivery dynamics and kinetics. To date, the development of a human model of the renal proximal tubule (PT) has been hindered by the lack of an appropriate cell source and scaffolds that allow epithelial monolayer formation and maintenance. Using extracellular matrices or matrix proteins, an in vivo-mimicking environment can be created that allows epithelial cells to exhibit their typical phenotype and functionality. Here, we describe an in vitro-engineered PT model. We isolated highly proliferative cells from cadaveric human kidneys (human kidney-derived cells [hKDCs]), which express markers that are associated with renal progenitor cells. Seeded on small intestinal submucosa (SIS), hKDCs formed a confluent monolayer and displayed the typical phenotype of PT epithelial cells. PT markers, including N-cadherin, were detected throughout the hKDC culture on the SIS, whereas markers of later tubule segments were weak (E-cadherin) or not (aquaporin-2) expressed. Basement membrane and microvilli formation demonstrated a strong polarization. We conclude that the combination of hKDCs and SIS is a suitable cell-scaffold composite to mimic the human PT in vitro.
authors.affiliation: 1 Department of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB) , Stuttgart, Germany .
authors.forename: Anke
authors.initials: A
authors.lastname: Hoppensack
authors.forename: Christian C
authors.initials: CC
authors.lastname: Kazanecki
authors.forename: David
authors.initials: D
authors.lastname: Colter
authors.forename: Anna
authors.initials: A
authors.lastname: Gosiewska
authors.forename: Johanna
authors.initials: J
authors.lastname: Schanz
authors.forename: Heike
authors.initials: H
authors.lastname: Walles
authors.forename: Katja
authors.initials: K
authors.lastname: Schenke-Layland
mesh_terms: D000943:Antigens, Differentiation / Q000096:biosynthesis; D051399:Aquaporin 2 / Q000096:biosynthesis; D040761:Biomimetic Materials / Q000737:chemistry*; D015820:Cadherins / Q000096:biosynthesis; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000737:chemistry*; D005786:Gene Expression Regulation; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000378:metabolism*; D008954:Models, Biological; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: C496023:AQP2 protein, human; D000943:Antigens, Differentiation; D051399:Aquaporin 2; D015820:Cadherins