Regeneration and experimental orthotopic transplantation of a bioengineered kidney

ORIGINAL: Nature

Jeremy J Song, Jacques P Guyette, Sarah E Gilpin, Gabriel Gonzalez, Joseph P Vacanti &Harald C Ott

14 April 2013

Nature Medicine 19, 646–651 (2013)

doi:10.1038/nm.3154

Received 04 September 2012

Accepted 11 February 2013

Published online 14 April 2013

Approximately 100,000 individuals in the United States currently await kidney transplantation, and 400,000 individuals live with end-stage kidney disease requiring hemodialysis. The creation of a transplantable graft to permanently replace kidney function would address donor organ shortage and the morbidity associated with immunosuppression. Such a bioengineered graft must have the kidney's architecture and function and permit perfusion, filtration, secretion, absorption and drainage of urine. We decellularized rat, porcine and human kidneys by detergent perfusion, yielding acellular scaffolds with vascular, cortical and medullary architecture, a collecting system and ureters. To regenerate functional tissue, we seeded rat kidney scaffolds with epithelial and endothelial cells and perfused these cell-seeded constructs in a whole-organ bioreactor. The resulting grafts produced rudimentary urine in vitro when perfused through their intrinsic vascular bed. When transplanted in an orthotopic position in rat, the grafts were perfused by the recipient's circulation and produced urine through the ureteral conduit in vivo.

Figure 1: Perfusion decellularization of whole rat kidneys. (a) Time-lapse photographs of a cadaveric rat kidney undergoing antegrade renal arterial perfusion decellularization. Shown are a freshly isolated kidney (left) and the same kidney after 6 h (middle) and 12 h (right) of SDS perfusion.

Figure 2: Perfusion decellularization of porcine and human kidneys.(a) Photograph of cadaveric (left) and decellularized (right) porcine kidneys suggesting that perfusion decellularization of rat kidneys can be upscaled to generate acellular kidney ECMs of clinically relevant size. Ra, renal artery; 

Figure 3: Cell seeding and whole-organ culture of decellularized rat kidneys. (a) Schematic of a cell-seeding apparatus enabling endothelial cell seeding through port A attached to the renal artery (Ra) and epithelial cell seeding through port B attached to the ureter (U) while negative pressure in the organ cham…