title: Development of a wearable bioartificial kidney using the Bioartificial Renal Epithelial Cell System (BRECS).
abstract: Cell therapy for the treatment of renal failure in the acute setting has proved successful, with therapeutic impact, yet development of a sustainable, portable bioartificial kidney for treatment of chronic renal failure has yet to be realized. Challenges in maintaining an anticoagulated blood circuit, the typical platform for solute clearance and support of the biological components, have posed a major hurdle in advancement of this technology. This group has developed a Bioartificial Renal Epithelial Cell System (BRECS) capable of differentiated renal cell function while sustained by body fluids other than blood. To evaluate this device for potential use in end-stage renal disease, a large animal model was established that exploits peritoneal dialysis fluid for support of the biological device and delivery of cell therapy while providing uraemic control. Anephric sheep received a continuous flow peritoneal dialysis (CFPD) circuit that included a BRECS. Sheep were treated with BRECS containing 1 × 108renal epithelial cells or acellular sham devices for up to 7 days. The BRECS cell viability and activity were maintained with extracorporeal peritoneal fluid circulation. A systemic immunological effect of BRECS therapy was observed as cell-treated sheep retained neutrophil oxidative activity better than sham-treated animals. This model demonstrates that use of the BRECS within a CFPD circuit embodies a feasible approach to a sustainable and effective wearable bioartificial kidney. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Innovative BioTherapies Incorporated, Ann Arbor, MI, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Johnston
authors.affiliation: Innovative BioTherapies Incorporated, Ann Arbor, MI, USA.
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Westover
authors.affiliation: The University of Michigan, Ann Arbor Section of Transplantation Surgery, Ann Arbor, MI, USA.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Rojas-Pena
authors.affiliation: Innovative BioTherapies Incorporated, Ann Arbor, MI, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Buffington
authors.affiliation: Innovative BioTherapies Incorporated, Ann Arbor, MI, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Pino
authors.affiliation: Innovative BioTherapies Incorporated, Ann Arbor, MI, USA.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Smith
authors.affiliation: Innovative BioTherapies Incorporated, Ann Arbor, MI, USA.|University of Michigan, Ann Arbor Department of Internal Medicine-Nephrology, Ann Arbor, MI, USA.
authors.forename: H David
authors.initials: HD
authors.lastname: Humes
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007688:Kidneys, Artificial; D012756:Sheep; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D000076251:Wearable Electronic Devices
keywords: artificial kidney; cell therapy; end-stage renal disease; kidney failure; peritoneal dialysis; sheep model