Tissue Engineering of a Bioartificial Renal Tubule

MacKay, Sherrill M.; Funke, Angela; Buffington, Deborah A.; Humes, H. David

doi:10.1097/00002480-199805000-00011

Cited by 97 publications

(56 citation statements)

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“…In experimental animals, the BAK developed by our group has shown important physiologic activity [25][26][27][28]. In vitro studies of the RAD have shown that the cells retain differentiated active transport properties, differentiated metabolic activities, and important endocrine processes [27].…”

Section: Discussionmentioning

confidence: 99%

“…Our laboratory has developed an extracorporeal device utilizing a standard hemofiltration cartridge containing over 10 9 human renal tubule cells grown as confluent monolayers along the inner surface of the fibers [25][26][27]. The nonbiodegradability and pore size of the hollow fibers allow the membranes to act as both scaffolds for the cells and as an immunoprotective barrier.…”

Section: Introductionmentioning

confidence: 99%

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Renal Cell Therapy in the Treatment of Patients with Acute and Chronic Renal Failure

Humes

Weitzel

Fissell³

2004

Blood Purif

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Hemodialysis and hemofiltration have been important technologies in saving the lives of patients with acute (ARF) and chronic renal failure by clearing small solutes from plasma and thereby preventing death from acidemia, hyperkalemia, volume overload, and uremia. These therapeutic approaches, however, are still suboptimal, as patients with ARF have mortality rates exceeding 50%, and patients with end-stage renal disease (ESRD) have, on average, a life expectancy of 4–5 years. The preeminent cause of death in patients with ARF is the development of sepsis or the systemic inflammatory response syndrome with resulting systemic vasodilation, hypotension, ischemic injury to solid organs, multi-organ failure, and death. This vasodilation is due to persistent and excessive pro-inflammation. Similarly, the reduced survival times of patients with ESRD on chronic dialysis have been associated with a persistent and chronic systemic pro-inflammatory state. We have hypothesized that the loss of renal tubule cell mass acutely in acute tubule necrosis and chronically in ESRD results in an immunologically dysregulated state leading to excessive pro-inflammation. The replacement of renal tubule cell function may thus change the current dismal prognosis of patients with these disorders. In this regard, this report presents the first patient ever treated with a bioartificial kidney consisting of a synthetic hemofilter in series with a renal tubule assist device (RAD) containing approximately 10⁹ human renal tubule cells. This treatment in a critically ill patient with multi-organ failure and ARF in the intensive care unit was associated temporally with improved cardiovascular parameters and enhanced native kidney function. Multiple systemic plasma cytokine levels and gene expression profiles of peripheral white blood cells were also temporally changed with cell therapy. Clinical trials in patients suffering from either ARF or ESRD are currently ongoing to evaluate the influence of the RAD on the inflammatory response in these groups of patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Renal Cell Therapy in the Treatment of Patients with Acute and Chronic Renal Failure

Humes

Weitzel

Fissell³

2004

Blood Purif

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“…Previous efforts in tissue engineering of the kidney have been directed toward the development of extracorporeal renal support systems made of biologic and synthetic components (107)(108)(109)(110)(111)(112)(113), and ex vivo renal replacement devices are known to be life-sustaining. However, there would be obvious benefits for patients with end-stage kidney disease if these devices could be implanted long term without the need for an extracorporeal perfusion circuit or immunosuppressive drugs.…”

Section: Kidneymentioning

confidence: 99%

Tissue Engineering, Stem Cells, and Cloning

Koh

Atala

2004

Journal of the American Society of Nephrology

153

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“…The method has its foundation in the ability to isolate and expand in culture tubule cells from adult kidneys (Humes and Cieslinski, 1992;Humes et al, 1996), which are then grown along the inner surface of the fibers in a standard hemofiltration cartridge (MacKay et al, 1998;Humes et al, 1999b;Nikolovski et al, 1999). Cell at-STEM CELL APPROACHES FOR THE TREATMENT OF RENAL FAILURE tachment to the membrane is promoted by first coating it with extracellular matrix molecules.…”

Section: Full Renal Replacementmentioning

confidence: 99%