Replacement of renal function in uremic animals with a tissue-engineered kidney

Abstract

Current renal substitution therapy with hemodialysis or hemofiltration has been the only successful long-term ex vivo organ substitution therapy to date. Although this approach is life sustaining, it is still unacceptably suboptimal with poor clinical outcomes of patients with either chronic end-stage renal disease or acute renal failure. This current therapy utilizes synthetic membranes to substitute for the small solute clearance function of the renal glomerulus but does not replace the transport, metabolic, and endocrinologic functions of the tubular cells. The addition of tubule cell replacement therapy in a tissue-engineered bioartificial kidney comprising both biologic and synthetic components will likely optimize renal replacement to improve clinical outcomes. This report demonstrates that the combination of a synthetic hemofiltration device and a renal tubule cell therapy device containing porcine renal tubule cells in an extracorporeal perfusion circuit successfully replaces filtration, transport, metabolic, and endocrinologic functions of the kidney in acutely uremic dogs.

The Kidney and Uremic Toxin Removal: Glomerulus or Tubule?

“…transporter expressing cells to better mimic normal renal function and improve clinical outcomes for this patient population. 40 Clearly, there is still much ground for the transporter field to cover, but the very fact that such concepts are being discussed within the context of actually being able to practically achieve them 41 foreshadows some exciting times to come.…”

Proliferating Cells versus Differentiated Cells in Tissue Engineering

“…Experimental data shows that it is not yet possible to create functional tissues under in vitro conditions. [10][11][12][13] The major methodical obstacle appears to be the belief that cellular proliferation is always desirable.…”

Hollow Fiber Bioreactor Technology for Tissue Engineering Applications

“…Humes et al presented the first concept of using HFs for renal cells in 1999 (38,39). Porcine renal proximal tubule cells (PTCs) were cultured on the inner surface side of a single HF.…”