Architecture is Important! The Hepregen Blog

HepatoPac Provides the Most Accurate Predictivity in Both Your Long-Term AND Short-Term Experiments

Posted by Yvonne Aratyn-Schaus on Jul 2, 2015 10:43:04 AM

If you’ve been following the Hepregen blog and reading up on Hepregen’s products, HepatoPac® and HepatoMune™, you may be aware of the fact that we often point out the value of the unprecedented and unmatched longevity and stability of functionality exhibited by our micropatterned, co-culture platform.  This extended in vitro functionality (stable cytochrome P450 and Phase II enzymatic activity, albumin & urea production, transporter function enables investigation of the metabolism and transport of low turnover compounds and of chronic toxicity that simply cannot be performed in traditional short-lived culture systems, such as S9 fractions, microsomes, hepatic cell lines, or even primary hepatocytes that are not in a co-cultured, micropatterned configuration.

It is also noteworthy that the optimal metabolic activity that characterizes Hepregen’s micropatterned platform makes it the ideal liver model for obtaining the most accurate data available for short-term evaluations of drug metabolism or for other screening applications.  HepatoPac outperforms traditional models, especially in their capacity to resolve major, circulating metabolites found in vivo.  This blog is intended to highlight just a few examples of the functional features of HepatoPac. These will include the ability to,

o   Generate major, in vivo circulating and excretory metabolites both early (hours) and late (days) post compound exposure

o   Resolve time-dependent (early and late) appearance of in vivo relevant metabolites across human and pre-clinical species (monkey, dog, rat) within a single experiment

o   Better predict in vivo hepatic clearance rates for high-, intermediate-, and low-turnover compounds

Read More

Topics: In vitro liver advanced

Where do liver cells come from? Kate asks the hard questions.

Posted by Katherine Sydney Cook on May 28, 2015 2:10:56 PM

Intro

I’ve worked at Hepregen now for almost two years and have never fully understood how cell-sourcing works.  I knew that we purchased primary hepatocytes and other cell types from vendors and that these cells are costly and precious, but didn’t really understand how they got from a live liver to a frozen vial.

I decided it was time to solve this mystery, for myself and for all of the other scientists and business people out there who are curious about what goes on behind the scenes with their cell-sourcing.

To do this, I reached out to one Rob Kaiser, a colleague at Triangle Research Labs.  Rob is Director of Operations at TRL and is intimately familiar with the process of preparing hepatocytes for cryopreservation and shipping to companies like Hepregen, who utilize these cells for research purposes. 

Rob was kind enough to research a bunch of questions that I sent him, and below are his responses.  I will say that once I started asking these questions, I found myself on a roll.  There were SO MANY unknowns!  If, after reading this entry, you think I’ve missed a question, please feel free to comment and ask.  I’m sure that Rob would be happy to help us all out.

Image Courtesy of TRL: http://triangleresearchlabs.net/hepatocyte-experts/why-our-hepatocytes-are-better/ 

Read More

Topics: In vitro liver assays, In vitro liver basics

SOT 2015 - Too Many Hepatocytes!

Posted by Katherine Sydney Cook on Apr 28, 2015 10:47:00 AM

Hepatocytes Everywhere

“Too many hepatocytes!”  That’s what one harried conference-goer said to me over his shoulder as he walked briskly past the Hepregen booth.  I had asked him, as I ask almost everyone that walks by and shows interest, “Do you do work with hepatocytes?”  I wouldn’t say that this man’s response was the overall impression that I gleaned from SOT 2015, but it was definitely one of many.  There were indeed numerous vendors touting their hepatocyte assay technology, and I could only help but imagine how one could seriously differentiate between all of them.

Read More

Topics: Scientific Meetings

The Top Five Things I Learned About In Vitro Cell Culture Work Coming From the World of Analytical Chemistry

Posted by Timothy Hyde on Feb 2, 2015 4:15:41 PM

Hi, my name is Tim Hyde and I am a business development manager here at Hepregen.  I’ve been with Hepregen for about a year and a half now, and continue learning from our determined scientists every day.  My background is in analytical chemistry, which I’m finding is really helpful with respect to a lot of the analytical components of our system.  However, there has certainly been a lot to learn in terms of cellular biology.  I’d like to share with you the top five things I’ve learned so far.

Coming from a fairly rigid universe, analytical chemistry, I’m familiar with many ways of mitigating variability.  In fact, there are calculations one can perform to assess variability.  The end goal in analytical chemistry is to minimize variability and come to a reproducible conclusion.  Ideally, we would like be able to run virtually identical experiments, no matter who runs them and where.  For example: Say I run one experiment here in Pennsylvania, and another person runs the exact same experiment, say, in Japan.  In a perfect world, the results would be identical. 

However, what is a “result”, really? 

  • First, we have data. 
  • Second, we have “how” the data was obtained. 
  • Third, we have how the data may have been processed. 
  • Fourth, we have the “human” variable. 
  • Finally, we have how the data is interpreted.  There are easily five to ten factors that influence how data are interpreted into results, and when you add “biology” into the equation, there are certainly more factors to consider!

All these things contribute to inter-laboartory and even intra-laboratory variation in results.

From my perspective, where variability, human influence, statistics and various methods of processing are front-of-mind, here are the top five things I have learned about in vitro cell culture that I’m sure any seasoned cell biologist will laugh at, but many people who now “do” cell biology (and come from some other background) may agree with.  Please let me know your experiences!

Read More

Topics: In vitro liver basics

1983 – Birth of the Co-culture, Lotus 1-2-3 and the Chicken McNugget

Posted by Katherine Sydney Cook on Dec 18, 2014 3:16:00 PM

 

Goodbye, 2014 – Hello, 1983

Figure 1 - Christiane Guguen-Guillouzo, inventor of the hepatocyte co-culture technology.  © Heparg.com 

We at Hepregen would like to commemorate the closing of 2014 by taking a look back at some important historical events that have shaped us as a company, and a people.  In particular, we’d like to explore 1983 – the year that the co-culture was invented!  As you may or may not know, our HepatoPac technology is an architected co-culture model based in part upon the concepts first detailed in the random co-culture configuration.  Without the important research that took place in 1983, we might not even be here!  So, it is with an eye towards respect of our elders that we take this journey through the year of the co-culture’s birth.

Read More

Topics: In vitro liver assays, HepatoPac Basics

Microchip Technology Applied to Liver Cells

Posted by Jared Broberg on Nov 19, 2014 3:14:43 PM

It’s incredible how far we as a species have come in miniaturizing our technology. The engineering required for this miniaturization is spectacular --- so why not try to utilize these same technologies in the biological sciences? That’s what we’ve done here at Hepregen, and the ramifications are astounding. I am referring to HepatoPac, the brainchild of Sangeeta Bhatia at MIT (the latest recipient of the Lemelson-MIT prize) and a dedicated team of highly trained specialists here at Hepregen HQ.  Using sophisticated micro-fabrication techniques derived from the semiconductor industry, we have created an incredible product that is highly functional and extremely convenient to use. 

My name is Jared, and I’m one of the engineers and manufacturing associates at Hepregen who manufactures this intricately detailed and optimized HepatoPac product. In this blog entry, I’d like to share with you a little bit about how it’s made.

Read More

Topics: HepatoPac Basics

What are the MIST Guidelines and why should you care?

Posted by Katherine Sydney Cook on Nov 4, 2014 11:30:00 AM

MIST Overview

The Metabolites in Safety Testing (MIST) guidelines were released in 2008 by the USDA, FDA and CDER.

http://www.fda.gov/OHRMS/DOCKETS/98fr/FDA-2008-D-0065-GDL.pdf

The guidelines are a suggested, FDA-endorsed list of practices for safety testing of new compounds before clinical trials.  Following the guidelines is not required, but strongly recommended.  Therefore, understanding what they are and what they say is important for any company seeking to gain FDA acceptance. 

Read More

Topics: In vitro liver basics, DMPK, HepatoPac Basics

Hepatocytes in HepatoPac® function WITHOUT the need for Matrigel®

Posted by Katherine Sydney Cook on Oct 16, 2014 5:53:00 PM

Traditional sandwich cultures need Matrigel

Matrigel is an extracellular matrix commonly used in sandwich cultures to establish adhesion, polarity and morphology of the cells.  Its heterogeneous composition includes structural proteins and growth factors.  Without this overlay, hepatocytes quickly lose their liver-like properties over time.

Read More

Topics: In vitro liver basics, HepatoPac Basics

Comments