Cell therapy of renal failure

Area of Science:

• Biomedical Engineering
• Nephrology
• Regenerative Medicine

Background:

• The kidney is the first organ with established long-term ex vivo substitutive therapies, including hemodialysis and transplantation.
• Current therapies like hemodialysis, while effective for solute clearance, do not fully replicate a functional kidney's survival benefits.
• Acute and chronic renal failure remain significant health challenges necessitating improved therapeutic strategies.

Purpose of the Study:

• To engineer a bioartificial kidney device that mimics the metabolic, endocrine, and immunologic functions of a native kidney.
• To evaluate the efficacy and survival benefits of this bioartificial kidney in preclinical models and early clinical trials.

Main Methods:

• Development of a bioartificial device integrating a conventional dialysis filter with a bioreactor containing engineered renal proximal tubule cells (10^9 cells).
• In vitro and ex vivo assessment of differentiated cell activity.
• Evaluation in large animal models of gram-negative sepsis and a Phase I clinical trial in acute renal failure.

Main Results:

• Demonstrated differentiated activity of engineered renal proximal tubule cells in vitro and ex vivo.
• The bioartificial kidney conferred a survival advantage in animal models of sepsis, potentially through inflammatory mediator modulation.
• Successful completion of a Phase I clinical trial in patients with acute renal failure.

Conclusions:

• The engineered bioartificial kidney shows potential to replicate key kidney functions beyond solute clearance.
• The device may offer survival benefits, particularly in critical conditions like sepsis, by modulating inflammatory responses.
• Early clinical data suggest the bioartificial kidney is a viable therapeutic approach for acute renal failure.