Tissue engineering of a bioartificial renal tubule.
Development of a bioartificial renal tubule with a confluent monolayer of renal epithelial cells supported on a permeable synthetic surface may be the first step to further optimization of renal substitution therapy currently used with hemodialysis or hemofiltration. Madin-Darby canine kidney cells, a permanent renal epithelial cell line, were seeded into the lumen of single hollow fibers. Functional confluence of the cells was demonstrated by the recovery of intraluminally perfused 14C-inulin that averaged >98.9% in the cell lined units vs <7.4% in the control noncell hollow fibers during identical pressure and flow conditions. The baseline absolute fluid transport rate averaged 1.4+/-0.4 microl/30 min. To test the dependency of fluid flux with oncotic and osmotic pressure differences across the bioartificial tubule, albumin was added to the extracapillary space, followed by the addition of ouabain, an inhibitor of Na+K+ adenosine triphosphatase, the enzyme responsible for active transport across the renal epithelium. Addition of albumin resulted in a significant increase in volume transport to 4.5+/-1.0 microl/30 min. Addition of ouabain inhibited transport back to baseline levels of 2.1+/-0.4 microl/30 min. These results are the first demonstration that renal epithelial cells have been grown successfully as a confluent monolayer along a hollow fiber, and exhibit functional transport capabilities. The next steps in constructing a bioartificial renal tubule successfully are to develop a multi-fiber bioreactor with primary renal proximal tubule cells that maintain not only transport properties but also differentiated metabolic and endocrine functions, including glucose and ammonia production, and the conversion of vitamin D3 to a more active derivative. A renal tubule device may add critical renal functional components not currently substituted for, thereby improving the treatment regimens for patients with acute and chronic renal failure.
MacKay
S M
SM
Department of Internal Medicine, University of Michigan and VA Medical Center, Ann Arbor 48109, USA.
Funke
A J
AJ
Buffington
D A
DA
Humes
H D
HD
D000818:Animals; D001187:Artificial Organs; D001692:Biological Transport; D001698:Biomedical Engineering / Q000379:methods; D002460:Cell Line / Q000637:transplantation; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007444:Inulin / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000637:transplantation*; D010042:Ouabain / Q000494:pharmacology; D051437:Renal Insufficiency / Q000628:therapy; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D010042:Ouabain; D007444:Inulin; D000254:Sodium-Potassium-Exchanging ATPase