Design engineering of a bioartificial renal tubule cell therapy device

The use of a bioartificial renal tubule device composed of renal proximal t ubule cells grown within a hollow fiber cartridge is a first step in engine ering a bioartificial kidney to provide more complete replacement therapy o f 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 hol low fiber cartridge, and the other with cells grown as a confluent monolaye r within the hollow fibers themselves. First, the oxygen requirements of po rcine renal proximal tubule cells were determined, both attached to microca rriers 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-2/1 0(6) cells/min for our cultured proximal tubule cells in suspension and no significant difference was seen with attached cells. Proximal tubule segmen ts 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 describ ing oxygen concentration profiles within the two device configurations. Fro m 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 f luid flow distribution and determine optimal device configuration and geome try to decrease areas of low or stagnant flow.