Humes H D, Buffington D A, MacKay S M, Funke A J, Weitzel W F
Department of Internal Medicine, University of Michigan, VA Medical Center, Ann Arbor 48109, USA.
Nat Biotechnol. 1999 May;17(5):451-5. doi: 10.1038/8626.
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.
目前采用血液透析或血液滤过的肾脏替代疗法是迄今为止唯一成功的长期体外器官替代疗法。尽管这种方法维持了生命,但对于慢性终末期肾病或急性肾衰竭患者而言,其临床效果仍不尽人意,存在诸多不足。当前的这种疗法利用合成膜来替代肾小球的小分子溶质清除功能,但并未取代肾小管细胞的转运、代谢及内分泌功能。在包含生物和合成成分的组织工程化生物人工肾中加入肾小管细胞替代疗法,有望优化肾脏替代治疗,从而改善临床疗效。本报告表明,在体外灌注回路中,将合成血液滤过装置与含有猪肾小管细胞的肾小管细胞治疗装置相结合,成功替代了急性尿毒症犬肾脏的滤过、转运、代谢及内分泌功能。