Faculty Opinions recommendation of An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-parenchymal Cells.

Author(s):  
Catherine Verfaillie
2017 ◽  
Vol 9 (2) ◽  
pp. 490-498 ◽  
Author(s):  
Yuta Koui ◽  
Taketomo Kido ◽  
Toshimasa Ito ◽  
Hiroki Oyama ◽  
Shin-Wei Chen ◽  
...  

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Marko Gröger ◽  
Knut Rennert ◽  
Benjamin Giszas ◽  
Elisabeth Weiß ◽  
Julia Dinger ◽  
...  

Abstract Liver dysfunction is an early event in sepsis-related multi-organ failure. We here report the establishment and characterization of a microfluidically supported in vitro organoid model of the human liver sinusoid. The liver organoid is composed of vascular and hepatocyte cell layers integrating non-parenchymal cells closely reflecting tissue architecture and enables physiological cross-communication in a bio-inspired fashion. Inflammation-associated liver dysfunction was mimicked by stimulation with various agonists of toll-like receptors. TLR-stimulation induced the release of pro- and anti-inflammatory cytokines and diminished expression of endothelial VE-cadherin, hepatic MRP-2 transporter and apolipoprotein B (ApoB), resulting in an inflammation-related endothelial barrier disruption and hepatocellular dysfunction in the liver organoid. However, interaction of the liver organoid with human monocytes attenuated inflammation-related cell responses and restored MRP-2 transporter activity, ApoB expression and albumin/urea production. The cellular events observed in the liver organoid closely resembled pathophysiological responses in the well-established sepsis model of peritoneal contamination and infection (PCI) in mice and clinical observations in human sepsis. We therefore conclude that this human liver organoid model is a valuable tool to investigate sepsis-related liver dysfunction and subsequent immune cell-related tissue repair/remodeling processes.


2019 ◽  
Vol 8 (24) ◽  
pp. 1901379 ◽  
Author(s):  
Ceri‐Anne E. Suurmond ◽  
Soufian Lasli ◽  
Floor W. Dolder ◽  
Aly Ung ◽  
Han‐Jun Kim ◽  
...  

2020 ◽  
Author(s):  
Marion Duriez ◽  
Agnes Jacquet ◽  
Lucile Hoet ◽  
Sandrine Roche ◽  
Marie-Dominique Bock ◽  
...  

AbstractWe have developed an in vitro preclinical 3D Non-Alcoholic SteatoHepatitis (NASH) model by co-culturing four human primary liver cell types: hepatocytes, stellate, endothelial and Kupffer cells. Cells were embedded in a hydrogel of rat collagen in 96-well plate and a NASH-like environment was induced with a medium containing free fatty acids (FFAs) and tumor necrosis factor α (TNFα). This model was characterized by biochemical, imaging and transcriptomics analysis. On the one hand, we succeed in defining suitable culture conditions to maintain the 3D co-culture up to 10 days in vitro with the lowest level of steatosis, and reproducible low levels of inflammation and fibrosis. On the other hand, we induced NASH disease with a custom medium mimicking NASH features (hepatocyte injury, steatosis, inflammation and fibrosis). The 10-day cell viability and cost effectiveness of the model make it suitable for medium throughput drug screening and provide attractive avenues to better understand disease physiology and to identify and characterize new drug targets.SummaryWe developed a 3D human liver model which exhibits many features of non-alcoholic steatohepatitis and that could become a platform for medium throughput drug screening.


2011 ◽  
Vol 49 (01) ◽  
Author(s):  
SA Hoffmann ◽  
M Lübberstedt ◽  
U Müller-Vieira ◽  
D Knobeloch ◽  
A Nüssler ◽  
...  

2008 ◽  
Author(s):  
Cheng J. Cao ◽  
Gunda Reddy ◽  
Desmond I. Bannon ◽  
Mark S. Johnson

Author(s):  
Reza Afrisham ◽  
Sahar Sadegh-Nejadi ◽  
Reza Meshkani ◽  
Solaleh Emamgholipour ◽  
Molood Bagherieh ◽  
...  

Introduction: Obesity is a disorder with low-grade chronic inflammation that plays a key role in the hepatic inflammation and steatosis. Moreover, there are studies to support the role of exosomes in the cellular communications, the regulation of metabolic homeostasis and immunomodulatory activity. Accordingly, we aimed to evaluate the influence of plasma circulating exosomes derived from females with normal-weight and obesity on the secretion of inflammatory cytokines in human liver cells. Methods: Plasma circulating exosomes were isolated from four normal (N-Exo) and four obese (O-Exo) women. The exosomes were characterized and approved for CD63 expression (common exosomal protein marker) and morphology/size using the western blot and TEM methods, respectively. The exosomes were used for stimulation of HepG2 cells in vitro. After 24 h incubation, the protein levels of TNF-α,IL-6, and IL-1β were measured in the culture supernatant of HepG2 cells using the ELISA kit. Results: The protein levels of IL-6 and TNF-α in the cells treated with O-Exo and N-Exo reduced significantly in comparison with control group (P=0.039 and P<0.001 respectively), while significance differences were not found between normal and obese groups (P=0.808, and P=0.978 respectively). However, no significant differences were found between three groups in term of IL-1β levels (P=0.069). Based on the correlation analysis, the protein levels of IL-6 were positively correlated with TNF-α (r 0.978, P<0.001). Conclusion: These findings suggest that plasma circulating exosomes have probably anti-inflammatory properties independently from body mass index and may decrease the secretion of inflammatory cytokines in liver. However, further investigations in vitro and in vivo are needed to address the anti-inflammatory function of N-Exo and O-Exo in human liver cells and/or other cells.


1981 ◽  
Vol 193 (3) ◽  
pp. 811-818 ◽  
Author(s):  
T Ludolph ◽  
E Paschke ◽  
J Glössl ◽  
H Kresse

Enzymic cleavage of beta-N-acetylglucosamine residues of keratan sulphate was studied in vitro by using substrate a [3H]glucosamine-labelled desulphated keratan sulphate with N-acetylglucosamine residues at the non-reducing end. Both lysosomal beta-N-acetylhexosaminidases A and B are proposed to participate in the degradation of keratan sulphate on the basis of the following observations. Homogenates of fibroblasts from patients with Sandhoff disease, but not those from patients with Tay–Sachs disease, were unable to release significant amounts of N-acetyl[3H]glucosamine. On isoelectric focusing of beta-N-acetylhexosaminidase from human liver the peaks of keratan sulphate-degrading activity coincided with the activity towards p-nitrophenyl beta-N-acetylglucosaminide. A monospecific antibody against the human enzyme reacted with both enzyme forms and precipitated the keratan sulphate-degrading activity. Both isoenzymes had the same apparent Km of 4mM, but the B form was approximately twice as active as the A form when compared with the activity towards a chromogenic substrate. Differences were noted in the pH–activity profiles of both isoenzymes. Thermal inactivation of isoenzyme B was less pronounced towards the polymeric substrate than towards the p-nitrophenyl derivative.


Sign in / Sign up

Export Citation Format

Share Document