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To illustrate our last post dated April 18 about the note of the thematic think tank of the Inserm ethics committee on the ethical issues of the research on organoids, we put online this short video of Nantes University and Inserm showing the production of intestinal organoids (in French).

The organoid construction technique is one of the pillars of biofabrication. Organoids are research tools on biological processes and in particular the interaction of cells within an organ.

A thematic think-tank of the Inserm ethics committee examined the ethical issues of research on organoids. Anne Dubart-Kupperschmitt (UMR_S 1193), responsible for two “work-packages” of the iLite project (innovation in Liver tissue engineering - see here) was one of them. Among those interviewed, Jean-Charles Duclos-Vallée (see here), iLite scientific coordinator and chairman of the French Institute of BioFabrication.

We resume below the key points of the note from the working group:

• What characterizes an organoid as such is that it performs certain functions specific to the organ of which it is the organoid
• Organoids organize themselves, spontaneously
• An organoid does not have the same properties and functions as the organ. It is therefore not correct to speak of organoids as mini-organs

• Organoids are research tools that have no application in therapy yet
• It is not always well established that organoids are a good model for the diagnosis and evaluation of therapies
• The current lack, in most cases,of vascularity and / or innervation of these models produced in vitro is a limit which can pose serious problems

• What moral value should be given to living things consideredas a set of parts to be assembled?
• We observe the transitionfrom a natural order to an artificial order, namely theengineering of the living which for some is morally problematic in that it denotes an inappropriate attitude on our part
• Currently, there is no legal standard governing organoids which would make it possible in particular to determine with certainty who is the “owner” or “custodian” of this biological element.

• Science must guarantee a critical approach exercising vigilant control over its own forward-looking advances and committing to promise nothing that cannot be acted upon

Concerning the particular case of brain organoids (cerebroids):

• Characteristics such as sensitivity or awareness are crucial to define the moral status of cerebroids as well as that of any individualbeing
• The meaning given to the terms "emotion" and "consciousness" is essential for understanding the moral status of cerebroids
• If an electrical activity as such cannot be equivalent to consciousness or sensitivity, it cannot be excluded that an entity made up of neurons experiencesmental states since there are correlation and even causal relationshipsbetween mind or spirit and the brain
• Consciousness refers to a "network of consciousness" which is based on the brain's ability to maintain coherent brain dynamics. Thus it is the synchronization and the coherence of the interactions between the areas of the brain, condition not presently present at the level of the cerebroids in vitro, which makes it possible to be aware
• The identification of the means available to tacklethe issueof the moral status of animals in which human cerebroids will be transplanted must be considered in concrete terms

The text of the note from the Inserm ethics committee working group can be downloaded here and is available on HAL (open multidisciplinary archive) here or directly on the Inserm website here.

Launched at the initiative of IFBF in 2017, the course session "Tissue and organ bioengineering" of the doctoral school "Therapeutic innovation - from the fundamental to the applied" of Paris-Saclay University will be held on April 22, 23 and 24, 2020.

Experts from many health, education and research institutions,

• both French (AP-HP, CCML, CEA, Centrale-Supélec, Ecole Polytechnique, ENS Paris-Saclay, IFBF, Inserm, INSA, Institut Pasteur, Institut de la Vision, IRBA, INTS, Université Paris-Saclay, UTC),
• and foreign (Health Sciences Institute in Aragon, University of Edinburgh, Leuven, Tokyo, Twente),
• as well as companies (Biopredic, Cyprio, GoLiver, Sanofi, Treefrog),

will present the many specialties contributing to the new discipline of biofabrication:

• cell and organoid culture,
• matrices and "scaffolds",
• bio-printing,
• organs-on-a-chip,
• bio-artificial extracorporeal systems,
• preclinical and clinical applications,
• regulatory, economic and ethical aspects.

Please read the detailed program here.

On the "European Day of Organ Donation and Transplantation" of October 12, 2019, the European Commission published a general assessment for the year 2018.

Over 150,000 patients were waiting for an organ. 6,000 registered patients died.

The 47th congress of the European Society for Artificial Organs (ESAO) will be held at Brunel University in Uxbridge near London from the 8th till the 12th of Septembre 2020. 

L’EASO promotes tissue & organ support and regeneration by artificial organ technology.

Candidates for a communication (please read the organisers' welcome letter here) must submit their abstract before the 29th of February.

Please visit the web site of ESAO that of its congress

We are starting today a series of posts relating to the shortage of organs which does not allow to meet fully, far from it, transplant indications. The number of patients on waiting lists is increasing and is abating. Each year, patients die for lack of a transplant.

An article published in December 2018 in the "Journal of the American Society of Nephrology" draws "the terrible assessment of the kidney shortage" in the United States. The authors estimate that 126,000 patients suffer from end-stage kidney disease each year. Only 16% of them will be able to benefit from a transplant. The other 84% will remain on dialysis with a life expectancy of less than 5 years.

The article in English "The Terrible Toll of the Kidney Shortage" is available here, or directly on the Jasn website.

By analogy with the expressions in vivo and in vitro, the term in silico was introduced to describe the numerical methods which make it possible to simulate or model a biological phenomenon using computers. The in silico methods are complementary to in vivo and in vitro studies. They provide information that is useful for a good understanding of biological mechanisms.

The robustness of the model strongly depends on the experimental data on which it is based. The development of a model begins with the collection of reliable experimental data. This step is followed by the characterization of the structures with a view to connecting them to the experimental property studied. Data analysis tools are then used to guide the characterization and set up the model itself. Once the model has been developed and in order to estimate its predictive power, additional experimental data is required.

A forthcoming congress in Paris, from August 26 or 28, will bring together specialists in the discipline, in particular researchers who are participating in the iLite research project (see here).

The congress poster can be viewed here.

Save the dates for the VPH2020 Conference organized by Inria and partners in Paris, August 26-28 2020
http://vph-conference.org

British researchers and historians have made a 3-dimensional artificial copy of the vocal tract of Nesyamun, scribe and priest of the temple of Karnak in Thebes (now Luxor) who lived under the reign of Ramses XI (around 1099-1060 BC) .

They scanned his mummy, in excellent condition which hasd been kept in the Leeds City Museum since 1823. By combining the copied organ and an artificial larynx, they allowed Nesyamun to pronounce… a vowel, a sound that no one had heard for 3000 years. Nesyamun's last wishes seem to have been respected: the inscriptions on his sarcophagus indicate that he hoped to be able to address the gods again as he had done during his life.

This example illustrates the results that can be expected in terms of organ functioning by the combination of biological material (mummified in this case) and advanced technologies.

The article, which appeared in the journal Nature, is available here:

Synthesis of a Vocal Sound from the 3,000 year old Mummy, Nesyamun ‘True of Voice’

Inserm (Institut national de la santé et de la recherche médicale) is looking to hire an experienced scientist to lead stem cell research, develop a team and take part in projects in the field of liver bioengineering.

The place of work is in fully equipped premises within the Paul-Brousse Hospital campus next to the largest European center for liver transplantation (Centre Hépato-Biliaire) in Villejuif, south of Paris.

Please click below to access to the full proposal.

See the job offer

UMR-S 1174, a member of the iLite (innovations in Liver tissue engineering) project, aims at producing a functional biliary network which has been a missing element in all previous studies.

see the job offer

The French Institute of BioFabrication, with Université Paris-Sud and the Hepatinov Academic Hospital Department, releases its “Tissue & Organ Bioengineering” MOOC on the FUN platform. The MOOC is designed for students, scientists and anyone interested in learning about the recent advances and techniques in bioengineering of organs and tissues.

The MOOC flyer is available here:

Présentation-MOOC-Tissue-Organ-Bioengineering.pdf

In order to directly access to the MOOC on the FUN platform, please click here:

https://www.fun-mooc.fr/courses/course-v1:pasteur+96007+session01/about

The start-up Cyprio, created in 2017 and specialised in the production of hepatic and pancreatic cell spheroids offers a post-doc position !

See job offer - Cyprio

French companies and clinical researchers create a center of gravity for liver bioprinting.

On Wednesday, September 13th, Biopredic International and Cellenion unveiled a new joint “French Institute of BioFabrication” laboratory at Hospital Paul-Brousse in Villejuif (south of Paris).

Cellenion, a daughter company of Berlin based Scienion AG, is a specialist in fully automated printing of viable cells for applications in the fields of bio-printing and bio-analytics. Biopredic International, a company based in Rennes, is a world leader in the production of a large range of cells and associated products for industrial research applications, with focus in pharmacokinetics, toxicology and pharmacology studies.

“Being able to work using bioprinting technologies offering resolution down to single cell is a fundamental tool in biology, tissue engineering and regenerative medicine” said Guilhem Tourniaire, Directeur Général at Cellenion, “With Biopredic, we have found a partner with excellent cell-based products and deep expertise in liver tissues engineering. This new facility will enable close collaborations with world-class clinicians and researchers to drastically accelerate development in liver tissue bioengineering”.

« We are a very customer focused company. As such, we always seek to expand our portfolio of solutions across the latest platform technologies” states Christophe Chesné, Chief Executive Officer at Biopredic and adds “Cellenion’s new acoustic based bioprinting technology is very synergistic with our cell and cell culture capabilities. The expertise of both companies are highly complementary, and working together in a joint laboratory will extend the companies’ clinical reach far beyond what was possible today”.

In recognition to the instrumental role of the association CellSpace in enabling this joint laboratory opening, the laboratory was officially named “CellSpace”. This Paris-based association funded by donations is dedicated to build an international platform devoted to the construction of bioengineered tissues in order to address the shortage of organ suitable for transplantation.

“Cellspace is very pleased that two high tech and key commercial partners for regenerative liver sciences have settled in Villejuif and started joint activities in close proximity to patient care at Paul-Brousse Hospital“ states Prof. Dominique Franco, Founder and Chairman of Cellspace.

Cellenion, Biopredic, CellSpace and scientists at Paul-Brousse Hospital Campus are also members of the iLite (Innovations Liver Tissue Engineering) RHU project. iLite is a 5-year project funded by the National Research Agency (ANR), directed by professor Jean-Charles Duclos-Vallée, that gathers leading French researchers, clinicians and industrial partners to develop an external bio-artificial liver for acute liver failure patients, liver-on-a-chip platform for toxicology studies and, in the longer term, a transplantable bio-constructed liver. The joint laboratories of Cellenion and Biopredic are geared to accelerate research within the iLite consortium and establish new collaborations with researchers and clinicians at Paul-Brousse Hospital as well as other university hospitals in the region.

Cécile Legallais, a CNRS/Université de Technologie Compiègne (UTC) researcher, comments on her project of an external bio-artificial liver. UTC is a member of CellSpace and Mrs Legallais ‘s team participates in the iLite project (see below).

Listen to the interview on CNRS/la radio (in French, 0-11mn, 35-38mn)

The Commissariat à l’Energie Atomique (CEA) is one of the members of the iLiTE project (innovation in Liver Tissue Engineering) and recruits a post-doctoral research scientist in the fields of micropatterning and bioprinting.

The DHU Hepatinov is the coordinating structure of the iLiTE project for University Hospital Research in Health (RHU). It has just been awarded €8.5 million in funding for its innovation project for Liver Tissue Engineering.

The French Institute of BioFabrication, created at the initiative of Hépatinov, aims to build organs by bioengineering, and therefore represents Hépatinov in the execution of the iLite project. As such, The IFBF Institute is recruiting doctoral and post-doctoral researchers for the various work packages included in this project, namely:

* Imaging, image analysis, in silico models, and software generation (WP1)

* Liver tissue/organoids (WP2)

* Construction of biliary duct network (WP3)

 * In vitro construction of a vascular network (WP4)

* Integration of liver organoids into vascular and/or biliary networks and scale-up (WP5)

* Liver-on-chip (WP6)

* External bio-artificial liver (WP7)

* Safety/GMP/Industrialization (WP8)

The workplace will be mainly in the Paris region but some positions are also available in the provinces. The first recruitments are scheduled for early October 2016. To apply, write by email to:

* Professor Jean-Charles Duclos-Vallée, Hépatinov Coordinator, « jean-charles.duclos-vallee@ifbf-Institute.org »

* Professor Dominique Franco, IFBF Institute President, « dominique.franco@ifbf-Institute.org »

The international jury of the RHU (University Hospital Health Research) second call for projects of the Future Investments Program decided to fund 10 projects of which iLiTE (innovations in Liver Tissue Engineering).

The RHU program supports translational projects involving academic research, hospitals and businesses. The 10 funded projects will help strengthen the links between basic research with clinical but also industrial applications, and are part of the national strategy for research and health designed by the Government.

iLiTE (innovations in Liver Tissue Engineering), the driver of which is the Hepatinov DHU, brings together teams of the Paul-Brousse and Saint-Louis hospitals, University of Paris Saclay, CEA, INSERM,  INRIA and four companies. All these actors are members of CellSpace who pooled their energies and ambitions. This achievement confirms the validity of the CellSpace strategy to bring together the expertise in medecine, biology, physical sciences and engineering in order to encourage the creation of bioengineered organs.

See the press release (French)

As part of the “semaine de l’industrie” event (http://www.entreprises.gouv.fr/semaine-industrie), held from the 16th to the 20th of March 2016, Dominique Franco, President of the French Institute of BioFabrication, gives a presentation on producing bioengineered organs, on Saturday, 19th of March, 2016, from 3.00 pm to 5.00 pm, in the premises of the Sup’Biotech school, 66 rue Guy Moquet in Villejuif.

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