title: Differentiated growth of human renal tubule cells on thin-film and nanostructured materials.
abstract: Over 300,000 Americans are dependent on hemodialysis as treatment for renal failure, and kidney transplantation is limited by scarcity of donor organs. This shortage has prompted research into tissue engineering of renal replacement therapy. Existing bioartificial kidneys are large and their use labor intensive, but they have shown improved survival compared to conventional therapy in preclinical studies and an US Food and Drug Administration-approved phase 2 clinical trial. This hybrid technology will require miniaturization of hemofilters, cell culture substrates, sensors, and integration of control electronics. Using the same harvesting and isolation techniques used in preparing bioartificial kidneys for clinical use, we characterized human renal tubule cell growth on a variety of silicon and related thin-film material substrates commonly used in the construction of microelectromechanical systems (MEMS), as well as novel silicon nanopore membranes (SNMs). Human cortical tubular epithelial cells (HCTC) were seeded onto samples of single-crystal silicon, polycrystalline silicon, silicon dioxide, silicon nitride, SU-8 photoresist, SNMs, and polyester tissue culture inserts, and grown to confluence. The cells formed confluent monolayers with tight junctions and central cilia. Transepithelial resistances were similar between SNMs and polyester membranes. The differentiated growth of human tubular epithelial cells on MEMS materials strongly suggests that miniaturization of the existing bioartificial kidney will be feasible, paving the way for widespread application of this novel technology.
authors.affiliation: Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Fissell
authors.forename: Sargum
authors.initials: S
authors.lastname: Manley
authors.forename: Angela
authors.initials: A
authors.lastname: Westover
authors.forename: H David
authors.initials: HD
authors.lastname: Humes
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Fleischman
authors.forename: Shuvo
authors.initials: S
authors.lastname: Roy
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D001698:Biomedical Engineering; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D017097:Electric Impedance; D006801:Humans; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000166:cytology; D007684:Kidney Tubules / Q000166:cytology* / Q000254:growth & development*; D008567:Membranes, Artificial; D049329:Nanostructures / Q000648:ultrastructure; D036103:Nanotechnology; D011091:Polyesters / Q000737:chemistry; D016062:Porosity; D017655:Silicon Compounds / Q000737:chemistry; D013379:Substrate Specificity
chemical_list: D001672:Biocompatible Materials; D008567:Membranes, Artificial; D011091:Polyesters; D017655:Silicon Compounds