For ethical and cost-related reasons, use of animals for the assessment of mode of action, metabolism and/or toxicity of new drug candidates has been increasingly scrutinized in research and industrial applications. Physiologically based pharmacokinetic (PBPK2) modeling is the most potent in silico tool used for extrapolation of pharmacokinetic parameters to animal or  human models from results obtained in vitro. Two dimensional (2D) cell cultures have been a part of drug development for many years.

Nowadays, their role is decreasing in favor of three-dimensional (3D) cell cultures and co-cultures. 3D cultures exhibit protein expression patterns and intercellular junctions that are closer to in vivo states in comparison to classical monolayer cultures. In vitro absorption, distribution, metabolism, and excretion assessment, as well as drug-drug interaction (DDI), are usually performed with the use of various cell culture based assays. Progress in in silico and in vitro methods can lead to better in vitro-in vivo extrapolation (IVIVE) outcomes and have a potential to contribute towards a significant reduction in the number of laboratory animals needed for drug research. As such, concentrated efforts need to be spent towards the development of an HTS in vitro platform with satisfactory IVIVE features.

Source : https://www.ncbi.nlm.nih.gov/pubmed/28811111

HCS Pharma, expert in cellular imaging & in vitro assay development for High Content Screening (HCS) & Analysis (HCA) has just acquired BIOMIMESYS® Technology, a biomimetic hydrogel scaffold based on biofunctionalized hyaluronic acid with extracellular matrix components for 3D cell culture.

If you have already used BIOMIMESYS® products, be aware that they will be available again in early 2018! If you do not know yet this technology, please let us know your interest.

Using BIOMIMESYS® Technology, HCS Pharma will also provide its expertise in HCS/HCA to evaluate the efficacy, mode of action, and safety of your therapeutic molecules on 3D cell models.

Ask us for a TC to know more about our services and products.

BIOMIMESYS® Plates’ assets:

  • Natural biofunctionnalized scaffold
  • Ready-to-use and easy to handle for highly reproducible experiments
  • Compatible with HTS & HCS
  • Use also for long term cultures & in vivo transplantation
  • Ease of cell retrieval, PCR & WB analysis

In a study published last October in the journal Stem Cell Research, Chandrasekaran et al. compared the induction of neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) obtained by 2D and 3D culture methods. Neural differentiation of five hiPSC lines was analyzed at the protein level by immunocytochemistry and flow cytometry to reveal the expression of various markers : NPC, neuronal, cortical layer and glial markers.

NPCs derived from human PSCs are often induced using 3D aggregates, because these systems are considered as efficient differentiation tools to induce PSCs into the neural lineage. However, according to the authors, no publication had directly compared 3D neural induction (sphere) with 2D neural induction (monolayer) in terms of cell numbers, gene expression profiles, proliferation rates, differentiation potential, cell fate and functionality.

They found no significant difference between the two induction methods – or the different genetic background cell lines – regarding early differentiation events (neuroepithelial commitment and formation of neural rosettes). However, a higher number of NPCs positive for NESTIN and PAX6 was generated using 3D neural induction, compared to the 2D method. Interestingly, the analysis of neurite length revealed that the 3D-induced neurons exhibited longer neurites than 2D-induced cells.

This study, among others, shows that 3D culture methods might help to improve the differentiation of human cells in vitro, leading to more physiological phenotypes !

As you can see below (in french), our CDO Grégory MAUBON is not a biologist, he is a astrophysicist 🙂 Of course it doesn’t matter because he has to explore best ways to build 3D pictures and how to extract most relevant parameters … in high throughput of course !

Find the complete article in french on Connected Report

We want to thanks Connected MagDanielle Roméro and Thomas Gouritin for this interview !

It’s always funny to see that the “old” maximum intensity projection is so used in picture reconstruction. Even if we all know artefacts created by this method, we often prefer a parameter free tool … In this article, a new way to do the 3D to 2D reduction is presented, the smooth manifold extraction, and it is compared to others one.

Three-dimensional fluorescence microscopy followed by image processing is routinely used to study biological objects at various scales such as cells and tissue. However, maximum intensity projection, the most broadly used rendering tool, extracts a discontinuous layer of voxels, obliviously creating important artifacts and possibly misleading interpretation. Here we propose smooth manifold extraction, an algorithm that produces a continuous focused 2D extraction from a 3D volume, hence preserving local spat

Source: Smooth 2D manifold extraction from 3D image stack | Nature Communications

From 28 March to 1st April, the conference on DYRK1A and related kinases and human disease was held in Saint Malo. We have really enjoyed our venue as a sponsor of this conference. Thanks to the organizers, specially to Laurent Meijer and Pauline Demaison, we had a chance to present our services to the scientific community working on DYRKs protein. During 3 days, we have seen a lot of high quality scientific presentations from chemistry to the development of treatments for DYRKs related disease. We hope all these talks from international researchers will lead to scientific improvements in DIRK related disease.

The development of cellular models, especially in neurotoxicity, is an approach used to accelerate the development of new therapeutics for DYRK related disease. With our progress in 3D models, HCS Pharma hopes to provide new tools for researchers to better understand DYRKs protein,  and perhaps participate as a speakers at the next DYRK conference !

To see our assay in neurotoxicity just click here : http://hcs-pharma.com/services/toxicology/neurotox/

3D cell models are now attracting a huge interest from scientists working both on toxicity and pharmacology assay development. They are considered more relevant at mimicking the in vivo situation. However, phenotypic assays on these models can be challenging, and are at least more complex.

A team from Molecular Devices and Cellular Dynamics has worked on the “phenotypic characterization of toxic compound effects on liver spheroids derived from iPSC using confocal imaging an three-dimensional image analyis”. The results have been published September 2016 in Assay and Drug Development Technologies, and describe how the ImageXpress Micro Confocal High-Content Imaging System and MetaXpress High-Content Image and Analysis Software (Molecular Devices) were used to manage the phenotypic characterization.

Assuming that the approach may be extensible to more complex 3D systems, such as cultures containing multiple cell types (e.g., Kuppfer cells, fibroblasts, endothelial cells), they conclude 3D analysis would allow characterization of different cell populations and their roles in toxicity and liver injury.

Source : Phenotypic Characterization of Toxic Compound Effects on Liver Spheroids Derived from iPSC Using Confocal Imaging and Three-Dimensional Image Analysis

It’s very interesting to show that, at HCS Pharma, we work on many of the most exciting medical technologies identified by Dr. Bertalan Mesko on his blog, medicalfuturist.com. Of course, precision medicine is the most important for us, because we see here extraordinary tools to treat cancer and neurodegenerative diseases (“instead of canons, we start using sniper rifles.”)

But two other fields seem really promising. The 3D bioprinting for exemple will give us the possibility to create relevant in vitro models of living tissues. We also work to integrate IA deep learning in our HCS processes. It will be a major method to find phenotypic actions of futur drugs.

2016 was a rich year for medical technology. Virtual Reality. Augmented Reality. Smart algorithms analysing wearable data. Amazing technologies arrived in our lives and on the market almost every day. And it will not stop in the coming year.

Source: The Most Exciting Medical Technologies of 2017 – The Medical Futurist

ESTIV conference, named In Vitro Toxicology for Human Safety Assessment, takes place this week in Juan-les-Pins. This congress brings together a lot of toxicologists, from public and private, to discuss the last development of predictive in vitro models in safety testing, as 3D models, organ-on-a-chip, bioprint organs.

To learn more and to exchange on these topics, Julian, our COO, is present to this conference. Have a nice time to discuss with him on these last development of in vitro safety testing models ! If you want to be contacted, please leave your mobile number here :

We just begin a test period of the Operetta “High Content Imaging System” from Perkin Elmer. First impressions are very good, especially using confocal option for 3D imaging. As you can see below, neurites growth is quite easy to observe around and inside a spheroid of SH-SY5Y cells. To properly count it is more complicated for the moment but we progress in the mastering of “Harmony” and “Columbus” softwares, as for “Acapella” scripts. Our next challenge is to build comprehensive 3D visualisation with Volocity software.

More and more articles show the advantages of culture compared to 2D in field. This article describe how to do high throughput using 3D culture by rapid size profiling analysis over time on tumor spheroids.

“Tumor size is the most frequently used in vivo endpoint when assessing antitumor efficacy in animal xenograft models, whereas proliferation is the more typically evaluated growth endpoint in vitro using two-dimensional (2D) monolayer cultures. Such 2D in vitro assays frequently fail to correlate with in vivo observations, owing to the inability of 2D cultures to recapitulate the native tumor microenvironment described above. Three-dimensional (3D) tumor microtissues, or multicellular tumor spheroids, are considered a more representative, organotypic model for assessment of tumor growth. They contain layers of cells that exhibit more in vivo-like size- and gradient-dependent proliferation and viability profiles.”

To know more about this article, follow this link: http://www.genengnews.com/gen-articles/phenotypic-drug-discovery-in-3d/5303/

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