Evaluation of bioartificial renal tubule device prepared with lifespan-extended human renal proximal tubular epithelial cells

Saitō, Akira; Sawada, Kaichiro; Fujimura, Satoshi; Suzuki, Hajime; Hirukawa, Takashi; Tatsumi, Rei; Kanai, Genta; Takahashi, Hiroo; Miyakogawa, Takayo; Sanechika, Noriyuki; Fukagawa, Masafumi; Kakuta, Tsunekazu

doi:10.1093/ndt/gfr755

Cited by 22 publications

(27 citation statements)

References 36 publications

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“…Here, we studied release of IL‐6, IL‐8 and IL‐10 from the bioreactor after perfusion with 10 μg/ml of LPS for 24 hrs or after perfusion with normal medium not containing LPS. LPS administration was performed in two of the previous in vivo studies where changes in cytokine levels were observed and one study used E. coli administration. The conditions under which the other in vivo studies and the clinical trial were performed could not be mimicked in vitro .…”

Section: Resultsmentioning

confidence: 99%

“…Cytokine levels in serum and plasma were measured in various animal studies and the Phase I/II clinical trial . Some changes in cytokine levels suggested that beneficial effects of BAK treatment might be a result of immunomodulatory functions . However, the release of cytokines or other immunomodulators from the bioreactor unit has not been investigated, so far.…”

Section: Introductionmentioning

confidence: 99%

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A novel design of bioartificial kidneys with improved cell performance and haemocompatibility

Kandasamy

Tasnim

et al. 2013

J Cellular Molecular Medi

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Treatment with bioartificial kidneys had beneficial effects in animal experiments and improved survival of critically ill patients with acute kidney injury in a Phase II clinical trial. However, a Phase II b clinical trial failed. This and other results suggested various problems with the current design of bioartificial kidneys. We propose a novel design to improve various properties of device, including haemocompatibility and cell performance. An important feature of the novel design is confinement of the blood to the lumina of the hollow fibre membranes. This avoids exposure of the blood to the non-haemocompatible outer surfaces of hollow fibre membranes, which usually occurs in bioartificial kidneys. We use these outer surfaces as substrate for cell growth. Our results show that commercial hollow fibre membranes can be directly applied in the bioreactor when human primary renal proximal tubular cells are grown in this configuration, and no coatings are required for the formation of robust and functional renal epithelia. Furthermore, we demonstrate that the bioreactor unit produces significant amounts of interleukins. This result helps to understand the immunomodulatory effects of bioartificial kidneys, which have been observed previously. The novel bioartificial kidney design outlined here and the results obtained would be expected to improve the safety and performance of bioartificial kidneys and to contribute to a better understanding of their effects.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A novel design of bioartificial kidneys with improved cell performance and haemocompatibility

Kandasamy

Tasnim

et al. 2013

J Cellular Molecular Medi

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“…Many studies have shown that levels of serum cytokines, such as TNF-α and IL-6, are increased in patients with severe AKI [14–16]. Pro-inflammatory cytokines may contribute to additional organ dysfunction, which is associated with high mortality [17].…”

Section: Discussionmentioning

confidence: 99%

Effects of continuous renal replacement therapy on serum cytokines, neutrophil gelatinase-associated lipocalin, and prognosis in patients with severe acute kidney injury after cardiac surgery

Wang

et al. 2016

Oncotarget

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The aim of our study was to evaluate the effect of continuous renal replacement therapy (CRRT) on serum cytokines, neutrophil gelatinase-associated lipocalin (NGAL), and prognosis in patients with severe acute kidney injury (AKI) following cardiac surgery. A total number of 153 patients with severe AKI following cardiac surgery were treated with CRRT. They were divided into the survival and non-survival groups. Clinical data from these two groups before and after CRRT were recorded and analyzed. It was found that the number of impaired organs, MODS and APACHE II scores were significantly higher in the non-survival group than those in the survival group before CRRT. After CRRT, MODS and APACHE II scores decreased significantly. The post-CRRT levels of serum TNF-a and IL-6 were significantly decreased. After CRRT, serum NGAL decreased in the two groups, but the levels were higher in the non-survival group than those in the survival group. MODS and APACHE II scores could be used to evaluate the severity of AKI in patients after cardiac surgery. CRRT is an effective treatment for these patients and high levels of TNF-a, IL-6, and NGAL are associated with a poor prognosis in these patients.

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“…Importantly, clinical trials using this approach reported better survival and more rapid recovery from AKI [69,70]. Saito et al also reported a bioartificial renal tubule device that reduces the expression levels of inflammatory cytokines and increased the life span of AKI goats [71]. These results suggest bioartificial devices may diminish the morbidity and mortality of AKI patients [72,73], but the type(s) of renal tubule cells used needs further consideration.…”

Section: Bioartificial Kidneymentioning

confidence: 99%

Novel regenerative therapy for acute kidney injury

Toyohara

Osafune

2016

Ren Replace Ther

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Acute kidney injury (AKI) is a renal disease that is associated with high mortality. Current treatments mostly rely on supportive therapies and do not directly target the disease. Regenerative medicine, however, offers potentially direct AKI therapy through two strategies: cell transplantation and kidney reconstruction. Regarding cell transplantation, several cell types are potential sources, including hematopoietic stem cells, mesenchymal stem cells, and renal stem/progenitor cells within the adult kidney tissue or derived from human-induced pluripotent stem cells (iPSCs). On the other hand, kidney reconstruction could provide a curative treatment for severe AKI and consequent chronic kidney disease (CKD). Many methods have been proposed for the kidney reconstruction, including self-organization, blastocyst complementation, decellularization, and bioartificial kidneys. However, there are still a number of obstacles to overcome before reconstructed kidneys reach clinical use. In this review, we summarize the recent progresses in cell transplantation and kidney reconstruction as strategies to treating AKI.

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Evaluation of bioartificial renal tubule device prepared with lifespan-extended human renal proximal tubular epithelial cells

Abstract: BTD treatment results in less damage from endotoxin shock and increased life span in AKI goats. These results suggest that BTD may be a useful component of bioartificial kidneys and should be considered in the next generation of renal replacement therapies.

Cited by 22 publications

References 36 publications

A novel design of bioartificial kidneys with improved cell performance and haemocompatibility

A novel design of bioartificial kidneys with improved cell performance and haemocompatibility

Effects of continuous renal replacement therapy on serum cytokines, neutrophil gelatinase-associated lipocalin, and prognosis in patients with severe acute kidney injury after cardiac surgery

Novel regenerative therapy for acute kidney injury

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