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Formation of bile tubes in a 3D culture system


Researchers from Inserm UMR_S1193 at Paul Brousse Hospital in Villejuif led by Anne Dubart-Kupperschmitt (see here), member of the IFBF Scientific Committee, have shown, as part of the iLite University Hospital Research project ( innovations in Liver tissue engineering), that induced human pluripotent cells (hiPSCs) could be differentiated into cholangiocytes capable of self-assembly to form bile tubes in a three-dimensional culture system. The active transport of a fluorescent bile acid analog has shown the functionality of the tubes formed, demonstrating the potential of these structures in a bioconstruction approach.

The article detailing the protocol appeared last July in Methods in Cell Biology volume 159 (see here).

2020 10 10 Equipe ADK dans lescalier

The team with Prof. Duclos-Vallée, scientific manager of the iLite project

Organoids: created in vitro but as close as possible to living tissues


The “Quotidien du Médecin” reports in an article published on September 8 (see here) of its interviews with several organoid specialists, in particular Anne Dubart-Kupperschmitt, member of the IFBF Scientific Council (see here) and Jean-Charles Duclos-Vallée, president of the Institute (see here).

Researchers and clinicians have highlighted the great interest that organoids represent for the understanding of diseases (currently Covid-19, see our post of June 26), the development of new molecules, the regeneration of tissues and the transplantation of organs. They also mentioned the challenges they face, that of vascularity in the first place.

Particular emphasis has been placed on liver organoids capable of reproducing large numbers of organ functions, the total of which exceeds 500. The article ends with the mention of the test on small animals of a hepatic bioreactor, one of the objectives of the iLite project (see here).

Tissue engineering and the pandemic


After Nature (see the news dated June 26, 2020), the New York Times echoes the use of tissue engineering, and in particular bioprinting, to test pharmaceutical molecules.

"...Anthony Atala, the director of the Wake Forest Institute for Regenerative Medicine, and his team are creating tiny replicas of human organs — some as small as a pinhead — to test drugs to fight Covid-19.

The team is constructing miniature lungs and colons — two organs particularly affected by the coronavirus — then sending them overnight by courier for testing at a biosafety lab at George Mason University in Fairfax, Va...

In the past few years, Dr. Atala’s institute had already printed these tiny clusters of cells to test drug efficacy against bacteria and infectious diseases like the Zika virus, “but we never thought we’d be considering this for a pandemic,” he said. His team has the ability to print “thousands an hour,” he said from his lab in Winston-Salem, N.C."

The New York Times open access article can be viewed here or on the newspaper's website here.

A taste of the future


KFC, the fast-food chain, announced that it is taking a new step towards its “restaurant of the future” by targeting the production of chicken meat by bio-printing. KFC has just signed a cooperation agreement with 3D Bioprinting Solutions, a Russian company that gained recognition in 2018 by testing its technology on board the International Space Station. The partners set themselves the goal of biofabricated chicken "nuggets"the appearance and taste of which will be as close as possible to those of the original product. The first biofabricated "nuggets" will be available this fall.

KFC's press release is available here.

Tissue and Organ Bioengineering doctoral course


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 could not be held in April due to the covid-19 crisis.

It will be held on Monday the 21st, Wenesday the 23rd and Thursday the 24th of September 2020 as a webinar.

Experts from many health, education and research institutions,

  • both French (AP-HP, CEA, Ecole Polytechnique, IFBF, Inserm, Institut Pasteur, Institut de la Vision, IRBA, Université Paris-Saclay, UTC),
  • and foreign (Health Sciences Institute in Aragon) 

as well as from a company (Sanofi),

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,
  • regulatory, economic and ethical aspects.

Please read the detailed program here.

Segway founder wants to revolutionize biofabrication


Dean Kamen, the creator of the Segway, founded the Advanced Regenerative Manufacturing Institute, a non-profit organization with approximately 170 members, companies and academic research institutions and endowed with $ 300 million.

His objective is "to collect extraordinary people that have different backgrounds, that probably don’t interact now, but if they did would dramatically accelerate the path to a major breakthrough.” in order to manufacture  replacement organs in the next 10 years.

The article from the web publication OneZero is available on its website here or downloadable here.

SARS-CoV-2 and organoids


Organoids are three-dimensional multicellular structures that partially replicate the anatomy of an organ in vitro. They represent an essential field of research in biofabrication. They can be the basic building blocks for making a tissue or bioartificial organ. They are also very useful tools for understanding illnesses and developing their treatments.

This article published in Nature relates the use of lung, but also kidney, liver anc intestine, organoids in the study of COVID-19, especially in the case of its most serious cases. Likewise, these organoids greatly facilitate the initial toxicology tests with a view to developing a treatment.

The article from Nature, freely accessible, can be read on the journal's website here, or downloadable here.

Researchers produce a model of the early embryonic brain


Research on brain development in the embryo involves many teams. That of the Department of Neuroscience at the University of Copenhagen, in collaboration with biotechnology engineers from the University of Lund in Sweden, publishes in Nature Biotechnology an article proposing a model based on a microfluidic system. The use of this technology lays the foundations for the use of 3D tissues for toxicological analysis.

The press release from the University of Copenhagen is available here.

The link to the article is here.

The production of intestinal organoids


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 research on organoids: which ethical issues?


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.

 

Tissue and Organ Bioengineering doctoral course


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.

Organ shortage (2)


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.

 

2018 EU Shortage of organs

47th congress of the European Society for Artificial Organs (ESAO)


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

Organ shortage (1)


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.

Virtual Physiological Human


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

 

Une voix du passé : Nesyamun, scribe et prêtre du temple de Karnak, s’adresse à nous.


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’

Poste de Maître de Conférence enseignant à l'ENS Paris-Saclay


HepaRG self‐assembled spheroids in alginate beads meet the clinical needs for bioartificial liver


Unique opportunity for an experienced scientist in stem cell biology to develop a team in the field of liver bioengineering for the construction of liver organoids


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

Morphogenèse de canaux biliaires dans des supports naturels et artificiels


GoLiver Therapeutics a les honneurs de la presse.


Inserm & Paris-Saclay UMR-S 1174 offers a post-doctoral position.


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

“Tissue & Organ Bioengineering” MOOC: registration is open!


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

Cyprio recruitment


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