Bioartificial Renal Epithelial Cell System (BRECS): A Compact, Cryopreservable Extracorporeal Renal Replacement Device

Abstract

Renal cell therapy has shown clinical efficacy in the treatment of acute renal failure (ARF) and promise for treatment of end-stage renal disease (ESRD) by supplementing conventional small solute clearance (hemodialysis or hemofiltration) with endocrine and metabolic function provided by cells maintained in an extracorporeal circuit. A major obstacle in the widespread adoption of this therapeutic approach is the lack of a cryopreservable system to enable distribution, storage, and therapeutic use at point of care facilities. This report details the design, fabrication, and assessment of a Bioartificial Renal Epithelial Cell System (BRECS), the first all-in-one culture vessel, cryostorage device, and cell therapy delivery system. The BRECS was loaded with up to 20 cell-seeded porous disks, which were maintained by perfusion culture. Once cells reached over 5 × 106 cells/disk for a total therapeutic dose of approximately 108 cells, the BRECS was cryopreserved for storage at −80°C or −140°C. The BRECS was rapidly thawed, and perfusion culture was resumed. Near precryopreservation values of cell viability, metabolic activity, and differentiated phenotype of functional renal cells were confirmed post-reconstitution. This technology could be extended to administer other cell-based therapies where metabolic, regulatory, or secretion functions can be leveraged in an immunoisolated extracorporeal circuit.

Challenges and Advances in the Treatment of AKI

“…The bioartificial renal epithelial cell system, BRECS, was developed for this intent-a device that functions as a combined bioreactor, cryostorage device, and cell therapy device. 36 …”

Bioengineered Renal Cell Therapy Device for Clinical Translation

“…4 The Bioartificial Renal Epithelial Cell System (BRECS) is a cell-based device that was developed to enable distribution for potential therapeutic use via cryopreservation. 5 An initial design of the BRECS made by Computer Numerical Control (CNC) machining (herein referred to as a CNC-BRECS), a perfusion bioreactor was able to support adult progenitor derived renal cells cultivated on porous disks, which could be cryopreserved as a complete device, thawed as a complete device, and employed in a therapeutic extracorporeal hemofiltration circuit. 5 The capability of cryopreservation, along with the use of an allogenic cell source in an immuno-isolated extracorporeal circuit, enables widespread availability of cell-based devices for on-demand therapy of acute disease states; however the initial CNC-BRECS (Figure 1 left) was not conducive to mass production.…”

“…5 An initial design of the BRECS made by Computer Numerical Control (CNC) machining (herein referred to as a CNC-BRECS), a perfusion bioreactor was able to support adult progenitor derived renal cells cultivated on porous disks, which could be cryopreserved as a complete device, thawed as a complete device, and employed in a therapeutic extracorporeal hemofiltration circuit. 5 The capability of cryopreservation, along with the use of an allogenic cell source in an immuno-isolated extracorporeal circuit, enables widespread availability of cell-based devices for on-demand therapy of acute disease states; however the initial CNC-BRECS (Figure 1 left) was not conducive to mass production. Herein, the design and testing of BRECS rapid prototypes created by stereolithography (SLA-BRECS, Figure 1 middle) are presented, to arrive at a finalized injection molded (IM-BRECS, Figure 1 right) design which overcomes hurdles associated with mass production and distribution for clinical translation of cell therapy.…”

Creating a wearable artificial kidney: where are we now?

“…Developments in this area are still preliminary but exciting, and will likely coincide with advances in kidney regeneration and tissue reengineering [19], although important challenges in terms of biocompatibility, immunogenicity, cell viability and effectiveness remain [20]. As an intermediate step, a wearable PD device, with a combination of sorbents and a scaffold with renal epithelial cells has been proposed (Bioartificial Renal Epithelial Cell System) [21], in order to improve the metabolic and immunomodulatory effects of dialysis treatment [18].…”