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Regeneration and experimental orthotopic transplantation of a bioengineered kidney.

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.

SUBMITTER: Song JJ

PROVIDER: S-EPMC3650107 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Regeneration and experimental orthotopic transplantation of a bioengineered kidney.

Song Jeremy J JJ Guyette Jacques P JP Gilpin Sarah E SE Gonzalez Gabriel G Vacanti Joseph P JP Ott Harald C HC

Nature medicine 20130414 5

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. W ...[more]

PMID: 23584091

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Project description:BackgroundIt is necessity to maintain donor kidneys at a low temperature for laparoscopic orthotopic kidney transplantation (LOKT). We recently designed a controllable double-cycle cryogenic device (DCD) with a safer and more effective cooling setting. This study aimed to evaluate the safety and efficacy of this device in a swine model.MethodsA total of 20 pigs were procured for this study. We performed LOKT on 8 pigs using the controllable DCD for hypothermia, on another 8 pigs using the silicon tube cage (STC) for hypothermia, and on 4 pigs as the control group with no hypothermia measures (NH). The LOKTs were performed in autotransplantation mode in which the right kidney vein and artery were end-to-end anastomosed to the left kidney vein and artery in all three groups. The perioperative data, graft temperatures, and surgical complications were recorded, and histological examinations of kidney specimens were performed.ResultsThe average surface temperature in the DCD group (5±3.5 °C) was significantly lower than that in the STC (10±5.5 °C) and NH (28±3.0 °C) groups. In the DCD and STC groups, the temperature between the cooling setting and the adjacent peritoneum was 30±3.0 and 12±5.0 °C, respectively. All pigs survived for 7 days in the DCD group. In the STC group, 2 pigs died from liver lesions and other causes. A single pig had diabetes insipidus. No pigs survived for 7 days in the NH group. The specimens from pigs immediately after revascularization and from the surviving pigs on day 7 following transplantation showed that the morphology of the glomerular and renal tubules was largely normal in the DCD and STC groups. However, in the NH group, there was minimal interstitial and tubular oedema, and endothelial cell swelling occurred in some specimens immediately after revascularization. Pathological examination of the harvested graft specimens showed severe acute tubular necrosis in the NH group.ConclusionsThe newly designed controllable DCD can achieve the goal of cooling the kidney and warming the patient and may be a reliable, effective, inexpensive, and practical hypothermic maintenance system for LOKT in swine.

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Regeneration and experimental orthotopic transplantation of a bioengineered kidney.

Publications

Regeneration and experimental orthotopic transplantation of a bioengineered kidney.

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