Cell therapy of renal failure.
The kidney is unique in that it is the first organ for which long-term ex vivo substitutive therapy has been available. The first hemodialyzer was successfully applied to a human patient with acute renal failure in 1948, and the first successful allograft transplantation was performed with a kidney in 1951. Both treatments are used today. There is ample evidence that the small solute clearance function provided by hemodialysis does not confer the same survival advantage as a functional kidney, both in acute and in chronic renal failure. To mimic the metabolic, endocrine, and immunologic functions of the kidney, our group has successfully engineered a bioartificial device that includes a conventional dialysis filter and a bioreactor containing 10(9) renal proximal tubule cells. We have demonstrated differentiated activity of these cells both in vitro and ex vivo in a large animal model. The bioreactor has been shown to confer a survival advantage in two large animal models of gram-negative sepsis, seemingly due to modulation of inflammatory mediators. This bioartificial kidney has now completed a Phase I clinical trial in acute renal failure.
Fissell
W H
WH
Department of Internal Medicine, VA Medical Center, Ann Arbor, Michigan, USA.
Humes
H D
HD
D000818:Animals; D019149:Bioreactors; D017690:Cell Transplantation / Q000379:methods*; D017321:Clinical Trials, Phase I as Topic; D003928:Diabetic Nephropathies / Q000628:therapy*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000637:transplantation*; D023421:Models, Animal; D006435:Renal Dialysis