Design Engineering of a Bioartificial Renal Tubule Cell Therapy Device

The use of a bioartificial renal tubule device composed of renal proximal tubule cells grown within a hollow fiber cartridge is a first step in engineering a bioartificial kidney to provide more complete replacement therapy of renal function than is available today. In this study, the feasibility of...

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Main Authors: Janeta Nikolovski, Erdogan Gulari, H. David Humes
Format: Article
Language:English
Published: SAGE Publishing 1999-07-01
Series:Cell Transplantation
Online Access:https://doi.org/10.1177/096368979900800403
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author Janeta Nikolovski
Erdogan Gulari
H. David Humes
author_facet Janeta Nikolovski
Erdogan Gulari
H. David Humes
author_sort Janeta Nikolovski
collection DOAJ
description The use of a bioartificial renal tubule device composed of renal proximal tubule cells grown within a hollow fiber cartridge is a first step in engineering a bioartificial kidney to provide more complete replacement therapy of renal function than is available today. In this study, the feasibility of two designs for a tubule device were investigated: one with cells grown on microcarrier beads densely packed within the extracapillary space of a hollow fiber cartridge, and the other with cells grown as a confluent monolayer within the hollow fibers themselves. First, the oxygen requirements of porcine renal proximal tubule cells were determined, both attached to microcarriers and in suspension and compared to that of proximal tubule segments. The basal rate of cell respiration was found to be 2.29 ± 0.53 nmol O 2 /10 6 cells/min for our cultured proximal tubule cells in suspension and no significant difference was seen with attached cells. Proximal tubule segments displayed significantly higher respiratory rates. Cells were also found to be responsive in the presence of mitochondrial inhibitors or uncouplers, and their respiratory rates remained constant, despite multiple passaging. The resultant cell oxygen consumption parameter was used in models describing oxygen concentration profiles within the two device configurations. From these models, it was found that cells within our proposed device designs could theoretically be sustained and remain viable, with respect to oxygen limitations. Finally, flow visualization studies were performed to assess fluid flow distribution and determine optimal device configuration and geometry to decrease areas of low or stagnant flow.
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spelling doaj.art-415602976a69416888a8a2f0372e5a7d2022-12-22T01:10:51ZengSAGE PublishingCell Transplantation0963-68971555-38921999-07-01810.1177/096368979900800403Design Engineering of a Bioartificial Renal Tubule Cell Therapy DeviceJaneta Nikolovski0Erdogan Gulari1H. David Humes2Departments of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-2136Departments of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109-2136Internal Medicine and VA Medical Center, University of Michigan, Ann Arbor, MI 48109-2136The use of a bioartificial renal tubule device composed of renal proximal tubule cells grown within a hollow fiber cartridge is a first step in engineering a bioartificial kidney to provide more complete replacement therapy of renal function than is available today. In this study, the feasibility of two designs for a tubule device were investigated: one with cells grown on microcarrier beads densely packed within the extracapillary space of a hollow fiber cartridge, and the other with cells grown as a confluent monolayer within the hollow fibers themselves. First, the oxygen requirements of porcine renal proximal tubule cells were determined, both attached to microcarriers and in suspension and compared to that of proximal tubule segments. The basal rate of cell respiration was found to be 2.29 ± 0.53 nmol O 2 /10 6 cells/min for our cultured proximal tubule cells in suspension and no significant difference was seen with attached cells. Proximal tubule segments displayed significantly higher respiratory rates. Cells were also found to be responsive in the presence of mitochondrial inhibitors or uncouplers, and their respiratory rates remained constant, despite multiple passaging. The resultant cell oxygen consumption parameter was used in models describing oxygen concentration profiles within the two device configurations. From these models, it was found that cells within our proposed device designs could theoretically be sustained and remain viable, with respect to oxygen limitations. Finally, flow visualization studies were performed to assess fluid flow distribution and determine optimal device configuration and geometry to decrease areas of low or stagnant flow.https://doi.org/10.1177/096368979900800403
spellingShingle Janeta Nikolovski
Erdogan Gulari
H. David Humes
Design Engineering of a Bioartificial Renal Tubule Cell Therapy Device
Cell Transplantation
title Design Engineering of a Bioartificial Renal Tubule Cell Therapy Device
title_full Design Engineering of a Bioartificial Renal Tubule Cell Therapy Device
title_fullStr Design Engineering of a Bioartificial Renal Tubule Cell Therapy Device
title_full_unstemmed Design Engineering of a Bioartificial Renal Tubule Cell Therapy Device
title_short Design Engineering of a Bioartificial Renal Tubule Cell Therapy Device
title_sort design engineering of a bioartificial renal tubule cell therapy device
url https://doi.org/10.1177/096368979900800403
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