title: 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 × 106cells/disk for a total therapeutic dose of approximately 108cells, 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.
authors.affiliation: Innovative BioTherapies, Inc., Ann Arbor, MI, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Buffington
authors.affiliation: Innovative BioTherapies, Inc., Ann Arbor, MI, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Pino
authors.affiliation: Innovative BioTherapies, Inc., Ann Arbor, MI, USA.
authors.forename: Lijun
authors.initials: L
authors.lastname: Chen
authors.affiliation: Innovative BioTherapies, Inc., Ann Arbor, MI, USA.
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Westover
authors.affiliation: Innovative BioTherapies, Inc., Ann Arbor, MI, USA.
authors.forename: Gretchen
authors.initials: G
authors.lastname: Hageman
authors.affiliation: Innovative BioTherapies, Inc., Ann Arbor, MI, USA ; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA ; CytoPherx, Inc., Ann Arbor, MI, USA.
authors.forename: H David
authors.initials: HD
authors.lastname: Humes
keywords: Acute renal failure; Bioreactor; Cryopreservation; End-stage renal disease; Extracorporeal cell therapy; Progenitor