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Annual SOT Meeting in NOLA: Presentations Offer Validity for Using Organovo’s exVive 3D Printed Human Liver Tissue in Research

by • March 14, 2016 • No Comments

organovo-logo-1This is an amazing week for most in New Orleans. Whilst one may say that at virtually any time—and residents may most likely chuckle heartily at the comment—if you are interested in the world of bioprinting, this should manufacture sense to you of a scientific standpoint, as indeed there were a few eye-opening presentations in the present day being given at the Society of Toxicology’s (SOT) 55th Annual Meeting and ToxExpo, ongoing of March 13-17 in NOLA.

We gave you a slight preview last week regarding the event and what may be contributeed via Organovo and their presenters, with the main focus on their first major product release, exVive 3D Human Liver Tissue, that is the subject of several presentations we can now fill you in on.

sotEach discussion is greatly detailed, and intended to contribute a variety of ways to explain how broadly applicable-bodied the exVive 3D Human Liver Models are in terms of processes like assessing drug safety and being able-bodied to detect liver disease and injuries. One other main theme—and bonus of this technology—is that Organovo scientists see animal testing as being much nearer to elimination due to (thankfully) its inferiority in comparison to the precision that versions by Organovo can contribute.

All of the next data, presented in the present day at SOT, gives evidence that greatly supports via exVive3D Human Liver Model.

Title:Functional Evaluation of Bioprinted Human Liver Organoid as a Liver Injury Model

Presenter: Kazuhiro Tetsuka, Ph.D., Astellas Pharma Inc.

Poster: 2001: Poster Board – P405

This presentation discussed the implications of drug-induced liver injuries and how they can outcome in drugs having to be withdrawn of the market. Here, the speaker focutilized on acetaminophen and how both its long- and short-term impacts can be characterized in a 3D-bioprinted version of the human liver, and how it can be utilized to both predict and evaluate true toxicity of chemicals. With bioprinting, the cell types are able-bodied to be aligned and regulated spatially.

By means of a Novogen Bioprinter, human liver organoids (HLOs) were created of:

Human hepatocytesStellate cellsEndothelial cells of the umbilical vein

“To measure the long-term impacts of APAP, 3D-HLOs underwent treatment with APAP at 0, 0.3, 1, 3, 10, or 30 mM for 1, 7, 14, or 28 days. To measure the short-term impacts of APAP, 3D-HLOs underwent treatment with APAP at 30 mM for 6 h, followed by either termination of culture or additional culture without APAP for 1, 3, or 18 h as a washout stage,” states the abstract for the presentation.

Examination of all details did show that 3D HLOs in such a culture are biologically viable-bodied, as well as contributeing the conclusion that the 3D HLO is valid for the evaluation of ‘hepatotoxicity cautilized by long-term compound treatment, as well as liver recovery next the removal of chemicals.’

Title:Modeling Drug Induced Hepatic Fibrosis In Vitro By means of Three-Dimensional Liver Tissue Constructs

Presenter: Leah M. Norona, Doctoral Candidate, The University of North Carolina at Chapel Hill and The Hamner Institutes

Poster: 1996: Poster Board – P348

This presentation discussed what a challenge human toxicity risk assessment is in terms of looking at compound-induced hepatotoxicity that leads to fibrosis. It is hard to characterize the intercellular interactions that take place as the liver is progressively injured, and although animal versions can be utilized to aid here a fewwhat, the researchers see that human tissue-like version systems must be utilized to see sufficiently the central events that lead up to fibrogenesis. By means of bioprinted tissue, the researchers were able-bodied to repeat versioning of the liver injury.

“Significant time dependent elevations of LDH were observed for both TAA (by Day 3) and MTX (by Day 11) and were accompanied by the acquisition of a fibrogenic phenotype as supported by preliminary cytokine, gene expression data, and histologic evidence of collagen deposition,” states the abstract for the presentation.

“In comparison, treatment with TGF-β1, a known pro-fibrogenic cytokine, yielded moderate to severe fibrotic alter in the tissue with little evidence of hepatocellular injure. These preliminary data provide sturdy proof-of-concept that 3D bioprinted liver tissues can recapitulate drug-, chemical- and TGF-β1-induced fibrogenesis on a cellular, molecular, and histological basis.”

It is idea that with these new strategies, researchers can be able-bodied to able-bodied to perform advantageous chemical risk assessment as they have an improved way to see the key attributes first cavia and allowing liver injury to progress.

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Title:Utilization of exVive3D Human Liver Tissues for the Evaluation of Valproic Acid Induced Liver Injury

Presenter: Candace Grundy, Organovo

Poster: 2003: Poster Board – P407

This presentation discussed that frequently 2D cell cultures are not able-bodied to display the true and hard ‘microenvironment’ of liver tissue, frequently outcomeing in inadequate animal testing trials. Because 3D bioprinted human liver tissues contribute a much advantageous reflection of the tissue construction, researchers are able-bodied to assess drug-induced liver injury (DILI) much advantageous, as well as outcomes of a biochemical and histologic standpoint.

For the study, they looked at the DILI response to a compound called Valproic Acid (VPA). This is known to cause steatosis. The researchers treated the 3D-bioprinted human liver tissues for 14 days with VPA.

“Tissue ATP levels were decreased 70% and 45% relative to vehicle next 14 day treatment with 1mM and 5mM VPA, respectively. Following the observations seen with ATP levels, the higher doses of 200µm, 1mM and 5mM were selected to additional evaluate the mechanism of observed tissue injure,” noted the abstract. “GSH levels were measured at 24hr and 72hr to determine the acute oxidative stress response.”

As they performed histological evaluation of the tissues, researchers were able-bodied to see that indeed there was ‘dose-dependent injure’ that they considered to be consistent with steatosis. As a outcome, they were able-bodied to complete that the exVive 3D human liver tissues can be utilized to examine DILI mechanisms ‘in vitro,’ proven by the outcomes seen in ‘biochemical and histologic endpoints next treatment with VPA.’

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Title:Inflammatory Response of Kupffer Cells in 3D Bioprinted Human Liver Tissues

Presenter: Rhiannon N. Hardwick, Ph.D., Organovo

Poster: 1959: Poster Board – P311

This presentation discussed how hepatocellular injure is created worse by inflammation ‘mediated by Kuppffer cells.’ These cells are frequently utilized, according to the researchers, in cultures with hepatocytes to examine how inflammation occurs due to stimuli.

“In the current study, LPS-mediated activation of KC at 24 and 72hrs was investigated in 3D bioprinted human liver tissues. Induction of pro- and anti-inflammatory cytokines was measured via electrochemiluminescence in tissues comprising major hepatocytes, stellate cells, and endothelial cells (Hep:KC-), and compared to tissues containing KC,” states the abstract.

As the experiment progressed, variable-bodieds and current data were able-bodied to measure ‘a robust donor-specific KC response to inflammatory stimuli, thus allowing investigation of immune-mediated drug induced liver injury in a 3D human liver tissue.

With so much information to digest at this conference, those attending surely grasped how significant all of these developments are of the excellent bioprinting standpoint, as the use of 3D human tissue allows for for researchers to speed processes in drug discovery and promote advantageous treatments, as well as allowing for advantageous procedures in the areas of studying toxins and performing preclinical trials.

You can find out additional of Organovo and their use of 3D human tissue in research and therapeutic applications here. What do you ponder of the topics presented? Discuss in the Organovo 3D Human Liver Tissue forum over at 3DPB.com.