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Regeneration and experimental orthotopic transplantation of a bioengineered kidney

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TLDR
To regenerate functional tissue, rat kidney scaffolds are seeded with epithelial and endothelial cells and perfused these cell-seeded constructs in a whole-organ bioreactor, resulting in grafts that produced rudimentary urine in vitro when perfused through their intrinsic vascular bed.
Abstract
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.

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References
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Journal ArticleDOI

Morphometry of the renal corpuscle during normal postnatal growth and compensatory hypertrophy. A light microscope study.

TL;DR: Renal corpuscles from the juxtamedullary and subcapsular regions of the renal cortex were morphometrically analyzed in young rats and in adult rats that had been unilaterally nephrectomized or sham-operated at an early age, indicating hyperplasia among all populations of glomerular cells is indicated in normal growth, and to a greater extent in compensatory renal hypertrophy.
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Tubulogenesis from isolated single cells of adult mammalian kidney: clonal analysis with a recombinant retrovirus

TL;DR: Individual cells in the adult kidney have retained the ability for kidney tubuleogenesis in vitro, since cell lineage analysis with a recombinant retrovirus demonstrated that in vitro tubulogenesis arose from clonal expansion of a single cell.
Journal ArticleDOI

Prolongation of life in anephric rats following de novo renal organogenesis.

TL;DR: It is shown that survival of rats with all native renal mass removed can be increased by prior metanephros transplantation and ureteroureterostomy, the first demonstration that life can be extended following de novo renal organogenesis.
Journal ArticleDOI

Adhesion of rat glomerular epithelial cells to extracellular matrices: Role of β1 integrins

TL;DR: In rat GEC, alpha 2 beta 1 and/or alpha 3 beta 1 integrins appear to mediate adhesion to collagen I, collagen IV, and laminin, and the alpha 3beta 1 integrin is also the likely receptor for fibronectin, interacting through an RGD binding site.
Journal Article

Acute renal failure: prevailing challenges and prospects for the future.

TL;DR: The development of cell therapy with a renal tubule replacement device may add critical renal functional components not currently substituted with dialysis or hemofiltration, and the potential therapeutic advances which may occur as the authors enter the next century to treat this devastating clinical disease process have substantial promise.
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