A bio‐artificial renal epithelial cell system conveys survival advantage in a porcine model of septic shock

Westover, Angela J.; Buffington, Deborah A.; Johnston, Kimberly A.; Smith, Peter L.; Pino, Christopher J.; Humes, H. David

doi:10.1002/term.1961

Cited by 23 publications

(20 citation statements)

References 31 publications

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“…Furthermore, in the BRECS circuit, the uremic state can be controlled by modulating the small solute clearance through hemofiltration dose via a change in prefilter surface area, filtration rate, and flow rate to waste. In preclinical testing of the BRECS for the treatment of ARF caused by septic shock in a porcine model (17), PBRECS was demonstrated to be therapeutically efficacious in this extracorporeal circuit, along with improved cardiovascular performance and prolonged survival time (31). …”

Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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“…16 Results from this porcine model suggest that BRECS cell therapy delivered from an extracorporeal circuit exhibited therapeutic efficacy with improved cardiovascular performance and prolonged survival time compared with acellular controls. 17 …”

Section: Discussionmentioning

confidence: 99%

Bioengineered Renal Cell Therapy Device for Clinical Translation

et al. 2017

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The Bioartificial Renal Epithelial Cell System (BRECS), is a cell-based device to treat acute kidney injury through renal cell therapy from an extracorporeal circuit. To enable widespread implementation of cell therapy, the BRECS was designed to be cryopreserved as a complete device, cryostored, cryoshipped to an end-use site, thawed as a complete device, and employed in a therapeutic extracorporeal hemofiltration circuit. This strategy overcomes storage and distribution issues that have been previous barriers to cell therapy. Previous BRECS housings produced by Computer Numerical Control (CNC) machining, a slow process taking hours to produce one bioreactor, was also prohibitively expensive (>$600/CNC-BRECS); major obstacles to mass production. The goal of this study was to produce a BRECS to be mass produced by injection molding (IM-BRECS), decreasing cost (<$20/unit) and improving manufacturing speed (hundreds of units/hr), while maintaining the same cell therapy function as the previous CNC-BRECS, first evaluated through prototypes produced by stereolithography (SLA-BRECS). The finalized IM-BRECS design had a significantly lower fill volume (10 mL), mass (49 g) and footprint (8.5 cm×8.5 cm×1.5 cm), and was demonstrated to outperform the previous BRECS designs with respect to heat transfer, significantly improving control of cooling during cryopreservation and reducing thaw times during warming. During in vitro culture, IM-BRECS performed similarly to previous CNC-BRECS with respect to cell metabolic activity (lactate production, oxygen consumption and glutathione metabolism) and amount of cells supported.

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“…97 A major hurdle, however, in upscaling the RAD to commercial use is the lack of access to a reliable source of renal cells. 98 Organoid culture might provide a limitless, possibly autologous, cell source. Moreover, kidney organoids might function as a source of cells for decellu larized renal scaffolds.…”

Section: Therapymentioning

confidence: 99%

Development and application of human adult stem or progenitor cell organoids

et al. 2015

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Adult stem or progenitor cell organoids are 3D adult-organ-derived epithelial structures that contain self-renewing and organ-specific stem or progenitor cells as well as differentiated cells. This organoid culture system was first established in murine intestine and subsequently developed for several other organs and translated to humans. Organoid cultures have proved valuable for basic research and for the study of healthy tissue homeostasis and the biology of disease. In addition, data from proof-of-principle experiments support promising clinical applications of adult stem or progenitor cell organoids. Although renal organoids have many potential applications, an adult stem or progenitor cell organoid culture system has not yet been developed for the kidney. The development of such a system is likely to be challenging because of the intricate renal architecture. Differentiated 3D cultures and stem or progenitor cell 3D sphere cultures are, however, available for the kidney. These cultures indicate the feasibility of renal organoid culture and provide a solid basis for its development. In this Review, we discuss the state-of-the-art of human adult stem or progenitor cell organoid culture and the potential of renal organoids as tools in basic and clinical research.

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A bio‐artificial renal epithelial cell system conveys survival advantage in a porcine model of septic shock

Cited by 23 publications

References 31 publications

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

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

Bioengineered Renal Cell Therapy Device for Clinical Translation

Development and application of human adult stem or progenitor cell organoids

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