Heparin-based hydrogels induce human renal tubulogenesis in vitro

Acta Biomaterialia
Heather M WeberCarsten Werner

Abstract

Dialysis or kidney transplantation is the only therapeutic option for end stage renal disease. Accordingly, there is a large unmet clinical need for new causative therapeutic treatments. Obtaining robust models that mimic the complex nature of the human kidney is a critical step in the development of new therapeutic strategies. Here we establish a synthetic in vitro human renal tubulogenesis model based on a tunable glycosaminoglycan-hydrogel platform. In this system, renal tubulogenesis can be modulated by the adjustment of hydrogel mechanics and degradability, growth factor signaling, and the presence of insoluble adhesion cues, potentially providing new insights for regenerative therapy. Different hydrogel properties were systematically investigated for their ability to regulate renal tubulogenesis. Hydrogels based on heparin and matrix metalloproteinase cleavable peptide linker units were found to induce the morphogenesis of single human proximal tubule epithelial cells into physiologically sized tubule structures. The generated tubules display polarization markers, extracellular matrix components, and organic anion transport functions of the in vivo renal proximal tubule and respond to nephrotoxins comparable to the human ...Continue Reading

Citations

Jul 25, 2019·Faraday Discussions·Uwe FreudenbergCarsten Werner
Nov 2, 2019·Biomaterials Science·Dejan HusmanCarsten Werner
Jan 7, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Kun LeiXinling Wang
Mar 14, 2019·Archives of Toxicology·Dorina Diekjürgen, David W Grainger
Feb 28, 2019·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Chao HeChangsheng Zhao
Sep 22, 2020·Nature Reviews. Materials·Elizabeth A Aisenbrey, William L Murphy
Feb 24, 2021·ACS Applied Materials & Interfaces·Sophia SzymkowiakDavid L Kaplan
Mar 27, 2021·Chemistry : a European Journal·Han CuiJinghua Chen
May 15, 2020·Chemical Reviews·Carlos MotaLorenzo Moroni
Jul 5, 2021·Biological Chemistry·Sebastian KühnCarsten Werner

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