Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes

Shi, Xiaolei; Gao, Yimeng; Yan, Yupeng; Ma, Hucheng; Lu, Hui; Huang, Pengyu; Ni, Xuan; Zhang, Ludi; Zhao, Xin; Ren, Haozhen; Hu, Dan; Zhou, Yan; Tian, Feng; Ji, Yuan; Cheng, Xin; Pan, Guoyu; Ding, Yitao; Hui, Lijian

doi:10.1038/cr.2016.6

Cited by 106 publications

(88 citation statements)

References 35 publications

(67 reference statements)

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“…Observation of ammonia depuration is an evidence of hepatic synthetic function and is an important feature to propose the device we present here for clinical application[21,22]. When this MBR was challenged with an ammonia overload it showed an effective detoxification of this detrimental metabolite, either when cold preserved or fresh LMOs were examined.…”

Section: Discussionmentioning

confidence: 99%

Performance of cold-preserved rat liver Microorgans as the biological component of a simplified prototype model of bioartificial liver

Pizarro¹,

Mediavilla²,

Quintana³

et al. 2016

WJH

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AIMTo develop a simplified bioartificial liver (BAL) device prototype, suitable to use freshly and preserved liver Microorgans (LMOs) as biological component.METHODSThe system consists of 140 capillary fibers through which goat blood is pumped. The evolution of hematocrit, plasma and extra-fiber fluid osmolality was evaluated without any biological component, to characterize the prototype. LMOs were cut and cold stored 48 h in BG35 and ViaSpan® solutions. Fresh LMOs were used as controls. After preservation, LMOs were loaded into the BAL and an ammonia overload was added. To assess LMOs viability and functionality, samples were taken to determine lactate dehydrogenase (LDH) release and ammonia detoxification capacity.RESULTSThe concentrations of ammonia and glucose, and the fluids osmolalities were matched after the first hour of perfusion, showing a proper exchange between blood and the biological compartment in the minibioreactor. After 120 min of perfusion, LMOs cold preserved in BG35 and ViaSpan® were able to detoxify 52.9% ± 6.5% and 53.6% ± 6.0%, respectively, of the initial ammonia overload. No significant differences were found with Controls (49.3% ± 8.8%, P < 0.05). LDH release was 6.0% ± 2.3% for control LMOs, and 6.2% ± 1.7% and 14.3% ± 1.1% for BG35 and ViaSpan® cold preserved LMOs, respectively (n = 6, P < 0.05).CONCLUSIONThis prototype relied on a simple design and excellent performance. It’s a practical tool to evaluate the detoxification ability of LMOs subjected to different preservation protocols.

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Section: Discussionmentioning

confidence: 99%

Performance of cold-preserved rat liver Microorgans as the biological component of a simplified prototype model of bioartificial liver

Pizarro¹,

Mediavilla²,

Quintana³

et al. 2016

WJH

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“…However, the latest study by Shi et al . () on pigs showed that 3 hours of BAL treatment on the first day after the ALF induction increased the survival rate of pigs up to 87.5% compared to 12.5% in the nontreated ALF group. This suggests that a short‐time exposure of a BAL to patient plasma might already be enough to support patients, while diminishing the risk of ALF or ACLF plasma toxic effects on BAL biocomponents.…”

Section: Effects Of Plasma Of Alf or Aclf Patients On Bal Functionmentioning

confidence: 99%

Challenges on the road to a multicellular bioartificial liver

Starokozhko

Groothuis

2017

J Tissue Eng Regen Med

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Over recent years, the progress in the development of a bioartificial liver (BAL) as an extracorporeal device or as a tissue engineered transplantable organ has been immense. However, many important BAL characteristics that are necessary to meet clinical demands have not been sufficiently addressed. This review describes the existing challenges in the development of a BAL for clinical applications, highlighting multicellularity and sinusoidal microarchitecture as crucial BAL characteristics to fulfil various liver functions. Currently available sources of nonparenchymal liver cells, such as endothelial cells, cholangiocytes and macrophages, used in BAL development are defined. Also, we discuss the recent studies on the reconstruction of the complex liver sinusoid microarchitecture using various liver cell types. Moreover, we highlight some other aspects of a BAL, such as liver zonation and formation of a vascular as well as biliary network for an adequate delivery, biotransformation and removal of substrates and waste products. Finally, the benefits of a multicellular BAL for the pharmaceutical industry are briefly described.

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“…An artificial liver support system (ALSS) could be used as a bridge between liver failure and liver transplantation [5]. Before ALSS goes into clinical trials, establishment of an ideal experimental model in a large animal is desperately needed to test the feasibility, functionality, and safety [6, 7]. …”

Section: Introductionmentioning

confidence: 99%

Establishment of a Novel Simplified Surgical Model of Acute Liver Failure in the Cynomolgus Monkey

Cai

Weng

Feng

et al. 2016

BioMed Research International

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Models using large animals that are suitable for studying artificial liver support system (ALSS) are urgently needed. Presently available acute liver failure (ALF) models mainly involve pigs or dogs. Establishment of current surgical ALF models (hepatectomy/devascularization) requires either very good surgical skills or multistep processes—even multiple stages of surgery. Therefore, it is necessary to develop a simplified surgical method. Here we report a novel simplified surgical ALF model using cynomolgus monkeys. Six monkeys underwent portal-right renal venous shunt combined with common bile duct ligation and transection (PRRS + CBDLT). Postoperatively, the monkeys had progressively increased listlessness, loss of appetite, and obvious jaundice. Blood biochemistry levels (Amm, ALT, AST, TBiL, DBiL, ALP, LDH, CK, and Cr) and prothrombin time (PT) were significantly increased (all P < 0.01) and albumin (ALB) was markedly reduced (P < 0.01) compared with baseline values. Histological examination of liver specimens on postoperative day 10 revealed cholestasis and inflammation. PRRS + CBDLT produced ALF that closely correlated with clinical situations. Compared with other surgical or drug ALF models, ours was simplified and animals were hemodynamically stable. This model could provide a good platform for further research on ALSS, especially regarding their detoxification functions.

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Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes

Cited by 106 publications

References 35 publications

Performance of cold-preserved rat liver Microorgans as the biological component of a simplified prototype model of bioartificial liver

Performance of cold-preserved rat liver Microorgans as the biological component of a simplified prototype model of bioartificial liver

Challenges on the road to a multicellular bioartificial liver

Establishment of a Novel Simplified Surgical Model of Acute Liver Failure in the Cynomolgus Monkey

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