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 × 10 renal 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.

Fabrication of Kidney Proximal Tubule Grafts Using Biofunctionalized Electrospun Polymer Scaffolds

“…These devices include an extracorporeal cellular unit of renal proximal tubule epithelial cells, which express multiple transporters that cooperate in basolateral uptake and luminal excretion of various endogenous metabolites, including uremic toxins . FDA‐approved phase I/II clinical studies with a RAD suggested a potential added value of such a device in the treatment of critically ill subjects . The development, current status, and technical challenges of RADs have been extensively reviewed elsewhere .…”

Bioengineering strategies for nephrologists: kidney was not built in a day

“…To try to overcome these problems, the same research group developed a Bioartificial Renal Epithelial Cell System (BRECS) [57,58]. The BRECS technology, based on niobium-coated carbon and cryopreservable polycarbonate seeded with human renal tubular epithelial cells derived from adult progenitor cells, recently demonstrated efficacy when applied in series to a hemofilter in a porcine septic shock model [59] and as a wearable device connected to a peritoneal dialysis circuit in an anephric sheep model [60]. Although promising, the BRECS technology is yet to be applied in clinical trials.…”

From portable dialysis to a bioengineered kidney

“…One way to achieve this goal is to expand the functionality of conventional therapies by including cellular components capable of taking over tubular functions of the kidney, thus introducing the critical transport, metabolic, and endocrine functions of the kidney (Figure 2) [ [12][13][14]. In recent years, substantial progress has been made in the development of the BAK (Table 3) [61][62][63][64][65][66][67]. Because of the targeted high capacity clearance of PBUT, this approach is expected to result in considerable lowering of PBUT plasma concentrations [68], which may significantly reduce (cardiovascular) morbidity and mortality and increase quality of life [69].…”

“…Thus, elimination of a blood circuit, an inherent characteristic of HD-based therapy, would facilitate its development. One approach being explored is a wearable bioartificial kidney (WeBAK) for PD, a type of BRECS that uses peritoneal dialysate to provide oxygen and nutrients to the cells [67]. For uremic control sorbent technology is applied to regenerate the peritoneal dialysate, which is subsequently perfused through the BRECS, providing tubular cell functions [67].…”