Effect of human patient plasma ex vivo treatment on gene expression and progenitor cell activation of primary human liver cells in multi-compartment 3D perfusion bioreactors for extra-corporeal liver support

2009 ◽  
Vol 103 (4) ◽  
pp. 817-827 ◽  
Author(s):  
Eva Schmelzer ◽  
Kerim Mutig ◽  
Petra Schrade ◽  
Sebastian Bachmann ◽  
Jörg C Gerlach ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Liver ◽  
Progenitor Cell ◽  
Cell Activation ◽  
Ex Vivo ◽  
Liver Cells ◽  
Liver Support ◽  
Human Patient ◽  
Human Liver Cells ◽  
Perfusion Bioreactors

Primary Human Liver Cells as Source for Modular Extracorporeal Liver Support - a Preliminary Report

2002 ◽  
Vol 25 (10) ◽  
pp. 1001-1005 ◽  
Author(s):  
I.M. Sauer ◽  
K. Zeilinger ◽  
N. Obermayer ◽  
G. Pless ◽  
A. Grünwald ◽  
...  
Keyword(s):  
Human Liver ◽  
Treatment Time ◽  
Liver Perfusion ◽  
Cell Mass ◽  
Liver Weight ◽  
Liver Cells ◽  
Liver Support ◽  
Overall Treatment Time ◽  
Human Liver Cells ◽  
Extracorporeal Liver Support

Cell-based extracorporeal liver support is an option to assist or replace the failing organ until regeneration or until transplantation can be performed. The use of porcine cells or tumor cell lines is controversial. Primary human liver cells, obtained from explanted organs found to be unsuitable for transplantation, are a desirable cell source as they perform human metabolism and regulation. The Modular Extracorporeal Liver Support (MELS) concept combines different extracorporeal therapy units, tailored to suit the individual and intra-individual clinical needs of the patient. A multi-compartment bioreactor (CellModule) is loaded with human liver cells obtained by 5-step collagenase liver perfusion. A cell mass of 400 g – 600 g enables the clinical application of a liver lobe equivalent hybrid organ. A detoxification module enables single pass albumin-dialysis via a standard high-flux dialysis filter, and continuous venovenuous hemodiafiltration may be included if required. Cells from 54 human livers have been isolated (donor age: 56 ± 13 years, liver weight: 1862 ± 556 g resulting in a viability of 55.0 ± 15.9%). These grafts were not suitable for LTx, due to steatosis (54%), cirrhosis (15%), fibrosis (9%), and other reasons (22%). Out of 36 prepared bioreactors, 10 were clinically used to treat 8 patients with liver failure. The overall treatment time was 7–144 hours. No adverse events were observed. Initial clinical applications of the bioreactor evidenced the technical feasibility and safety of the system.

scholarly journals Improvement of therapeutic capacity of insulin-producing cells trans-differentiated from human liver cells using engineered cell sheet

2020 ◽  
Author(s):  
Yu Na Lee ◽  
Hye-Jin Yi ◽  
Eun Hye Seo ◽  
Jooyun Oh ◽  
Song Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Glucose ◽  
Human Liver ◽  
Cell Sheet ◽  
Liver Cells ◽  
Cell Sheets ◽  
Human Liver Cells ◽  
Insulin Producing Cells ◽  
Differentiation Efficiency

Abstract Background: Although pancreatic islet transplantation therapy is ideal for diabetes patients, several hurdles have prevented it from becoming a standard treatment, including donor shortage and low engraftment efficacy. In this study, we prepared insulin-producing cells trans-differentiated from adult human liver cells as a new islet source. Also, cell sheets formation could improve differentiation efficiency and graft survival.Methods: Liver cells were expanded in vitro and trans-differentiated to IPCs using adenovirus vectors carrying human genes for PDX1, NEUROD1 and MAFA. IPCs were seeded on temperature-responsive culture dishes to form cell sheets. Differentiation efficiency were confirmed by ß cell-specific gene expression, insulin production, and immunohistochemistry. IPCs suspension was injected by portal vein (PV), and IPCs sheet was transplanted on the liver surface of the diabetic nude mouse. The therapeutic effect of IPC sheet was evaluated by comparing blood glucose control, weight gain, histological evaluation and hepatotoxicity with IPCs injection group. Also, cell biodistribution was assessed by in vivo/ex vivo fluorescence image tagging.Results: Insulin gene expression and protein production were significantly increased on IPC sheets compared with those in IPCs cultured on conventional culture dishes. Transplanted IPC sheets displayed significantly higher engraftment efficiency and fewer transplanted cells in other organs than injected IPCs, and also lower liver toxicity, improved blood glucose levels, and weight gain. One and two weeks following IPC sheet transplantation, immunohistochemical analyses of liver tissue revealed positive staining for PDX1 and insulin.Conclusions: In conclusion, cell sheet formation enhanced the differentiation function and maturation of IPCs in vitro. Additionally, parameters for clinical application such as distribution, therapeutic efficacy, and toxicity were favorable. The cell sheet technique may be used with IPCs derived from various cell sources in clinical applications.

scholarly journals Low‐Dose Silver Nanoparticle Surface Chemistry and Temporal Effects on Gene Expression in Human Liver Cells

Small ◽  
2020 ◽  
Vol 16 (21) ◽  
pp. 2000299
Author(s):  
John S. House ◽  
Evangelia Bouzos ◽  
Kira M. Fahy ◽  
Victorino Miguel Francisco ◽  
Dillon T. Lloyd ◽  
...  
Keyword(s):  
Gene Expression ◽  
Surface Chemistry ◽  
Silver Nanoparticle ◽  
Human Liver ◽  
Low Dose ◽  
Liver Cells ◽  
Temporal Effects ◽  
Human Liver Cells ◽  
Nanoparticle Surface

scholarly journals Improvement of the therapeutic capacity of insulin-producing cells trans-differentiated from human liver cells using engineered cell sheet 

2020 ◽  
Author(s):  
Yu Na Lee ◽  
Hye-Jin Yi ◽  
Eun Hye Seo ◽  
Jooyun Oh ◽  
Song Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Weight Gain ◽  
Blood Glucose ◽  
Human Liver ◽  
Cell Sheet ◽  
Liver Cells ◽  
Cell Sheets ◽  
Human Liver Cells ◽  
Insulin Producing Cells

Abstract Background: Although pancreatic islet transplantation therapy is ideal for diabetes patients, several hurdles have prevented it from becoming a standard treatment, including donor shortage and low engraftment efficacy. In this study, we prepared insulin-producing cells trans-differentiated from adult human liver cells as a new islet source.Also, cell sheets formation couldimprove differentiation efficiencyand graft survival. Methods: Liver cells were expanded in vitro and trans-differentiated to IPCs using adenovirus vectors carrying human genes for PDX1, NEUROD1 and MAFA. IPCs were seeded on temperature-responsive culture dishes to form cell sheets. Differentiation efficiency were confirmed by ß cell-specific gene expression, insulin production, and immunohistochemistry. IPCs suspension was injected by portal vein (PV), and IPCs sheet was transplanted on the liver surface of the diabetic nude mouse.The therapeutic effect of IPC sheet was evaluated by comparing blood glucose control, weight gain, histological evaluation and hepatotoxicity with IPCs injection group. Also, cell biodistribution was assessed by in vivo/ex vivo fluorescence image tagging.Results: Insulin gene expression and protein production were significantly increased on IPC sheets compared with those in IPCs cultured on conventional culture dishes. Transplanted IPC sheets displayed significantly higher engraftment efficiency and fewer transplanted cells in other organs than injected IPCs, and also lower liver toxicity, improved blood glucose levels, and weight gain. Immunohistochemical analyses of liver tissue revealed positive staining for PDX1 and insulin at 1, 2 and 4 weeks after IPCs transplantation.Conclusions: In conclusion, cell sheet formation enhanced the differentiation function and maturation of IPCsin vitro. Additionally, parameters for clinical application such as distribution, therapeutic efficacy, and toxicity were favorable. The cell sheet technique may be used with IPCs derived from various cell sources in clinical applications.

scholarly journals Improvement of the therapeutic capacity of insulin-producing cells trans-differentiated from human liver cells using engineered cell sheet

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yu Na Lee ◽  
Hye-Jin Yi ◽  
Eun Hye Seo ◽  
Jooyun Oh ◽  
Song Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Weight Gain ◽  
Blood Glucose ◽  
Human Liver ◽  
Cell Sheet ◽  
Liver Cells ◽  
Human Liver Cells ◽  
Insulin Producing Cells ◽  
Differentiation Efficiency

Abstract Background Although pancreatic islet transplantation therapy is ideal for diabetes patients, several hurdles have prevented it from becoming a standard treatment, including donor shortage and low engraftment efficacy. In this study, we prepared insulin-producing cells trans-differentiated from adult human liver cells as a new islet source. Also, cell sheet formation could improve differentiation efficiency and graft survival. Methods Liver cells were expanded in vitro and trans-differentiated to IPCs using adenovirus vectors carrying human genes for PDX1, NEUROD1, and MAFA. IPCs were seeded on temperature-responsive culture dishes to form cell sheets. Differentiation efficiency was confirmed by ß cell-specific gene expression, insulin production, and immunohistochemistry. IPC suspension was injected by portal vein (PV), and IPC sheet was transplanted on the liver surface of the diabetic nude mouse. The therapeutic effect of IPC sheet was evaluated by comparing blood glucose control, weight gain, histological evaluation, and hepatotoxicity with IPC injection group. Also, cell biodistribution was assessed by in vivo/ex vivo fluorescence image tagging. Results Insulin gene expression and protein production were significantly increased on IPC sheets compared with those in IPCs cultured on conventional culture dishes. Transplanted IPC sheets displayed significantly higher engraftment efficiency and fewer transplanted cells in other organs than injected IPCs, and also lower liver toxicity, improved blood glucose levels, and weight gain. Immunohistochemical analyses of liver tissue revealed positive staining for PDX1 and insulin at 1, 2, and 4 weeks after IPC transplantation. Conclusions In conclusion, cell sheet formation enhanced the differentiation function and maturation of IPCs in vitro. Additionally, parameters for clinical application such as distribution, therapeutic efficacy, and toxicity were favorable. The cell sheet technique may be used with IPCs derived from various cell sources in clinical applications.

scholarly journals Gene expression profiles of human liver cells mediated by hepatitis B virus X protein

2009 ◽  
Vol 30 (4) ◽  
pp. 424-434 ◽  
Author(s):  
Wei-ying Zhang ◽  
Fu-qing Xu ◽  
Chang-liang Shan ◽  
Rong Xiang ◽  
Li-hong Ye ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Human Liver ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Liver Cells ◽  
X Protein ◽  
Human Liver Cells ◽  
B Virus

HBx or HCV core gene expression in HepG2 human liver cells results in a survival benefit against oxidative stress with possible implications for HCC development

2007 ◽  
Vol 168 (2) ◽  
pp. 128-134 ◽  
Author(s):  
Tamara Severi ◽  
Sara Vander Borght ◽  
Louis Libbrecht ◽  
Lucas VanAelst ◽  
Frederik Nevens ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Survival Benefit ◽  
Human Liver ◽  
Core Gene ◽  
Liver Cells ◽  
Human Liver Cells
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