Randomized Trial of Spheroid Reservoir Bioartificial Liver in Porcine Model of Posthepatectomy Liver Failure

Chen, Harvey S.; Joo, Dong Jin; Shaheen, Mohammed F; Li, Yi; Wang, Yujia; Yang, Jian; Nicolas, Clara T.; Predmore, Kelly; Amiot, Bruce; Michalak, Gregory J.; Mounajjed, Taofic; Fidler, Jeff L.; Kremers, Walter K.; Nyberg, Scott L.

doi:10.1002/hep.30184

Cited by 66 publications

(75 citation statements)

References 28 publications

(78 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…SRBAL makes use of a hollow fiber cartridge membrane to allow passage of toxins, proteins and other waste substances without exchange of larger blood components from the patient or hepatocytes from the SRBAL. In a previous preclinical study involving ALF pigs, SRBAL exhibited effective ammonia clearance associated with neuroprotection and a reduction in both intracranial pressure (ICP) and brain edema 8 , 9 . The possibility of xeno-zoonosis, such as porcine endogenous retrovirus (PERV) transmission, was not addressed in the prior study.…”

Section: Introductionmentioning

confidence: 99%

Novel spheroid reservoir bioartificial liver improves survival of nonhuman primates in a toxin-induced model of acute liver failure

Li¹,

Wu²,

Wang³

et al. 2018

Theranostics

Self Cite

View full text Add to dashboard Cite

This study aims to evaluate the effectiveness and safety of the spheroid reservoir bioartificial liver (SRBAL) with porcine hepatocyte organoids in a preclinical nonhuman primate model of acute liver failure (ALF).Methods: Thirty healthy rhesus monkeys were infused with α-amanitin and lipopolysaccharide and randomized into five groups (ALF alone control group; sham no-cell SRBAL treatment group; groups A, B and C with SRBAL treatment started at 12 h, 24 h and 36 h after induction of ALF, respectively). Animals were continuously treated with the SRBAL device for 6 h and followed for up to 336 h.Results: Survival of ALF monkeys improved with hepatocyte SRBAL treatment compared to control groups. Blood ammonia and total bilirubin were lower, and albumin levels were higher in all hepatocyte SRBAL treatment groups. No evidence of porcine endogenous retrovirus was identified in monkey liver or blood after SRBAL treatment. Titers of monkey antibody (IgG, IgM) did not rise after SRBAL treatment. In survival cases, the proportion of necrotic and apoptotic hepatocytes was lower in SRBAL-treated groups, with earlier liver regeneration leading to recovery. Cytokines TNF-α, IL-6, IL-12, IL-1β, IL-8, IFN-γ and IL-2 were ameliorated by the SRBAL treatment, while levels of M-CSF; HGF, EGF and VEGF; IL-1RA and MIF rose on priming, proliferation and the late phase of liver regeneration.Conclusions: The benefit of SRBAL therapy included preventive effects and therapeutic effects. SRBAL improved survival rate and prolonged median survival time in a nonhuman primate model of drug-induced ALF, and these benefits declined with a delay in the initiation of therapy. Improved survival and recovery of ALF monkeys was associated with a reduction in blood ammonia levels, inhibition of the pro-inflammatory response of ALF, and provided a microenvironment more suitable for regeneration of the injured liver.

show abstract

Section: Introductionmentioning

confidence: 99%

Novel spheroid reservoir bioartificial liver improves survival of nonhuman primates in a toxin-induced model of acute liver failure

Li¹,

Wu²,

Wang³

et al. 2018

Theranostics

Self Cite

View full text Add to dashboard Cite

show abstract

“…To our knowledge, no preclinical survival studies in large animals have been performed. The first large Improved survival time, neuroprotective benefit, improved biochemistry and accelerated liver regeneration [78] prospective CS in HBV-associated ACLF patients (MELD score 28-29) showed higher short-and long-term survival in the treatment group (n = 104) vs the control group (n = 130) [35].…”

Section: High Volume Plasma Exchangementioning

confidence: 99%

End-stage liver failure: filling the treatment gap at the intensive care unit

Chamuleau

Hoekstra

2019

J Artif Organs

View full text Add to dashboard Cite

End-stage liver failure is a condition of collapsing liver function with mortality rates up to 80. Liver transplantation is the only lifesaving therapy. There is an unmet need for therapy to extend the waiting time for liver transplantation or regeneration of the native liver. Here we review the state-of-the-art of non-cell based and cell-based artificial liver support systems, cell transplantation and plasma exchange, with the first therapy relying on detoxification, while the others aim to correct also other failing liver functions and/or modulate the immune response. Meta-analyses on the effect of non-cell based systems show contradictory outcomes for different types of albumin purification devices. For bioartificial livers proof of concept has been shown in animals with liver failure. However, large clinical trials with two different systems did not show a survival benefit. Two clinical trials with plasma exchange and one with transplantation of mesenchymal stem cells showed positive outcomes on survival. Detoxification therapies lack adequacy for most patients. Correction of additional liver functions, and also modulation of the immune system hold promise for future therapy of liver failure.

show abstract

“…Intrathecal delivery of autologous adipose-derived mesenchymal stem cells (Staff et al, 2016 ) Cell and cell based Liver failure Bioartifi cial liver (Chen et al, 2018 ) Bioengineered and hybrid Kidney failure Bioengineered vessel grafts for use in hemodialysis (Lawson et al, 2016 ) Bioengineered and hybrid Spinal cord injury Implantation of acellular injectable peripheral nerve matrix (Cerqueira et al, 2018 ) Acellular Breast cancer Acellular dermal matrix used for breast reconstruction (Sorkin et al, 2017 ) Acellular T lymphocytes technology paves the way for potentially curative options for certain cancers such as B-cell malignancies unresponsive to conventional treatment. Optimized stem cell therapy to treat heart failure utilizes cardioreparative cells developed to target the ailing myocardium (Terzic & Behfar, 2016 ).…”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

The Regenerative Horizon: Opportunities for Nursing Research and Practice

Chlan

Tofthagen

Terzic

2019

J of Nursing Scholarship

View full text Add to dashboard Cite

Background: Regenerative technologies aim to restore organ form and function. Technological advances in regenerative treatments have led to patients increasingly seeking these therapies. The readiness of nursing to fully contribute to this emerging healthcare field is uncertain. Purpose: The goal of this discipline-oriented overview is to enhance awareness in the nursing community regarding regenerative science, and to provide suggestions for nursing research contributions and practice implications. Methods: Evolving and applied cutting-edge therapies, such as regenerative immunotherapies with chimeric antigen receptor expressing T lymphocytes, are highlighted in the context of emerging opportunities for nurses in practice and research. Discussion: Next generation nurses will increasingly be at the forefront of new therapies poised to make chronic illnesses curable, thus restoring health and function to diverse groups of individuals. Clinical Relevance: The regenerative care model imposes on the nursing community the imperative to (a) increase research awareness; (a) educate, develop, and deploy a skilled nursing workforce; (c) integrate regenerative technologies into nursing practice; and (d) embrace the regenerative technologies horizon as a future in health care.

show abstract

Randomized Trial of Spheroid Reservoir Bioartificial Liver in Porcine Model of Posthepatectomy Liver Failure

Cited by 66 publications

References 28 publications

Novel spheroid reservoir bioartificial liver improves survival of nonhuman primates in a toxin-induced model of acute liver failure

Novel spheroid reservoir bioartificial liver improves survival of nonhuman primates in a toxin-induced model of acute liver failure

End-stage liver failure: filling the treatment gap at the intensive care unit

The Regenerative Horizon: Opportunities for Nursing Research and Practice

Contact Info

Product

Resources

About