Eric LECLERC, Dr.

 Eric Leclerc official picture Host Laboratory SAKAI LAB.
Position in LIMMS CNRS Senior Researcher
Main Research Topic in LIMMS

Bio-MEMS - Development of a new microscale culture model to investigate the differentiation and maturation of induced pluripotent stem (iPS) cells to hepatocytes

Keywords

iPS, hepatocytes, liver on chip, bioreactor

Contact LIMMS/CNRS-IIS (UMI 2820)
Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
Phone:+81 (0)3 5452 6036 / Fax:+81 (0)3 5452 6088
E-mail eleclerc at iis.u-tokyo.ac.jp
Download icon_pdf.gifAbstract2015_ELeclerc.pdf

Resume

Short resume :
2016-Present LIMMS French co-director
2015-Present CNRS senior researcher (Directeur de Recherche) in LIMMS
2013-2015 CNRS senior researcher (Directeur de Recherche) in BMBI (UMR 7338, UTC Compiegne)
2003-2013 CNRS junior researcher (Chargé de Recherche) in BMBI (UMR 7338, UTC Compiegne)

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Research Projects in Limms

1- Development of a new microscale culture model to investigate the differentiation and maturation of induced pluripotent stem (iPS) cells to hepatocytes
 

Context: Hepatocytes differentiated from induced pluripotent stem cells emerged as a promising source for in vitro liver model. iPS cells have two main properties, they may differentiate into all cell types that make up the body (pluripotency) and are able in ad hoc conditions to proliferate indefinitely in culture (self-renewal). Despite encouraging results, hepatocytes derived from iPS still present a differentiation pattern of primitiveness (AFP, SOX17) illustrating that the maturation is not completed. Different hypotheses can be formulated to explain the immaturity of these cells: (i) the absence of interaction between these cells and the other component liver cells; (ii) the lack of hemodynamic stresses in the system used; (iii) the lack of organ to organ interaction (iv) dilution of paracrine factors (PF) and growth factors (GF).

 

Objectives & Methods: The project liver-iPS on chip aims to develop, from hepatocytes derived from induced pluripotent stem cells (iPS), a microfluidic liver tissue culture model. The microfluidic bioreactor will provide 3D, dynamics and mass transfer nutrient control in a microconfined environment mimicking in vivo situations. 

 

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Overview of research activities in 2012-2015

The projects that I manage were coordinated in the Laboratory for Biomechanics and Bioengineering (UMR 7338, previously UMR 6600) of the University of Technology of Compiègne (UTC) until April 2015. Since April 2015 I joined the UMI 2820 in Tokyo, the Laboratory for Integrated Micro Mechatronics Systems.

 In 2003, I was recruited by the CNRS section 8 on a specific profile related to “microtechnology applications for biology and health”. In addition, due to the agreement between two CRNS departments (STIC and SPI) I was assigned to a laboratory that was interested by the targeted applications (rather than in a laboratory developing microdevices). Since 2003, within the UMR CNRS 7338, I have developed a new cell biochip activity and an “Applied Microfluidic and Cellular Microsystem” (MMC) team. This research team is transversal to the laboratory activity (C2B: cell biomaterial bioengineering; IFSB: fluid structures interaction in biology; C3M: multiscale characterization and model in mechanic; NSE: Neuro mechanic and electrophysiological signals). Two main topics were investigated in my MMC team:

 

-       Topic 1:  microfluidic biochips as new in vitro tools for predictive toxicology (transversal to C2B and NSE)

-       Topic 2:    microfluidic for characterization of tissue and soft matter (transversal to C2B and IFSB)

 

  In 2013, I was promoted to CNRS research director in section 28 on a project dealing with the development of the topic 1. Within this research topic, I introduced three themes that are:

 

            Theme 1: Human on chip approach that consists of developing miniaturized bio artificial organs to mimic the human physiology

            Theme 2: Integrative biology on chip that consists to use the biochips and systemic biology in an in vitro/ in vivo/ in silico strategy for predictive toxicology

            Theme 3: Integration of the biochip to move towards autonomous integrated analysis.

                      

 For both topics, I was the supervisor of the microfabrication and microfluidic platform that I developed. I was also the leader of the ‘Applied Microfluidic and Cellular Microsystem” (MMC) team which has been highlighted as an “emerging” theme in the laboratory structure since 2011. Between 2012 and April 2015, a research engineer of CNRS, a UTC technician, four post-doctoral fellows, five doctoral students and 3 long-term internships were directly involved in the team. The MMC team also interacts with various groups of the University (such as the team "soft and condense related matters" of EA TIMR, or such as “Decision and Images” of UMR 7253-HEUDIASYC and the “chaire de toxicologie predictive”). In addition, the developments of my projects are involved in the interactions resulting from the LABEX MS2T joining three laboratories of the University of Compiegne. In parallel, some of my projects are done the in the frame of the Tox / Ecotox program between UTC and INERIS related to the developments and the introduction of alternative methods to animal testing.

The activity has increased since its creation due to various grants managed. These funds are the result of research contracts (private and public). In 2012-2015, I supervised 11 contracts including one ANR project, one Labex MS2T project, one UTC-foundation grant, one ANSES project, and I was involved as partner in one ANR and one regional project. In parallel, we are discussing with industrials for common research projects and technology transfer (SATT Lutech).

 

 

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Platform management between 2011-2015

In parallel of the research activity, I have been involved in the development of a microfluidic and microfabrication platform of the UMR 7338. In January 2011, we have received a platform to perform biochip fabrication and microfluidic experiments. I was involved in the definitions of the rooms specifications. I was responsible for this area until April 2015. This platform is mostly equipped by facilities coming from the contract of my projects. This platform is used for microfabrication of polymer microchips and for microfluidic experiments. It completes the biological facilities that we used to perform the “cell biology on chips”. We mainly integrated facilities to extend the feasible material used in microfabrication, renew and revise the equipment, update the safety conditions, teach the users.

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Main publication List (papers, conferences and patent)

2016

Journals

 

  1. Zeller P, Legendre A, Jacques S, Fleury MJ, Gilard F, Tcherkez G, Leclerc E, "Hepatocyte-Sertoli cells coculture in bioreactor improves the Sertoli barrier permeability", Journal of Applied Toxicology, in press
  2. Jellali R, Duval JL, Leclerc E, "Analysis of the biocompatibility of perfluoropolyether dimethacrylate network using an organotypic method", in press
  3. Jellali R, Bricks T, Jacques S, Fleury MJ, Paullier P, Merlier F, Leclerc E, "Long term human primary hepatocyte cultures in a microfluidic liver biochip show maintenance of mRNA levels and higher drugs metabolisms when compared to Petri cultures", Biopharmaceutics and Drug Disposition, in press
  4. Jellali R, Paullier P, Fleury MJ , Leclerc E, "Liver and kidney cells cultures in a new perfluoropolyether biochip", Sensors and Actuators B. in press

 

Invited conferences

 

  1. Leclerc E, "Organs on chip in predictive toxicology and applied pharmacology", Micromachine Summit, May 2016, Tokyo, Japan
  2. Sakai Y and Leclerc E, "Engineering of hierarchical liver tissues using oxygen permeable plates and microfluidic", 23 HAB conference, May 2016, Tsukuba, Japan

 

International conferences with peer reviews

 

  1. Matsumoto S,Leclerc E, Maekawa T, Kinoshita H, Shinohara M, Komori K, Sakai Y, Fujii T, "Creation and Visualization of Oxygen Concentration in a Microfluidic Hepatocytes Culture Device", ISSM, 8th International Symposium on Microchemistry and Microsystems, 2016, Hong Kong, China

 

National conferences with peer reviews

 

  1. Matsumoto S,Leclerc E, Maekawa T, Kinoshita H, Shinohara M, Komori K, Sakai Y, Fujii T, "Verification of Visualization of Oxygen Concentration in a Microfluidic Hepatocytes Culture Device", Japan Society for Precision Engineering 2016 Spring conference (in Japanese), 2016, Tokyo, Japan

 

Patents

 

  1. Leclerc E, Kimura K, Sakai Y, Kido T, Miyajima A, "Method of differentiating pluripotent stem cells", PCT/FR2016/050523

 

2015

Journals

 

Invited conferences

 

  1. Leclerc E, "Development of microfluidic biochips in predictive toxicology and applied pharmacology", International congress of the alternative methods in animal experiements of Japanese society, 2015, Yokohama, Japan

 

International conferences with peer reviews

 

National conferences with peer reviews

 

  1. Leclerc E, "Glutathione systemic biology model coupled with microfluidic liver data for xenobiotic predictive toxicity", 33th Annual congress of the Japanese society of liver and hepatocytes, 2015, Tottori, Japan
  2. Matsumoto S, Maekawa T, Leclerc E, Sakai Y, Fujii T, "Formation of Oxygen Concentration Gradient in a Microfluidic Hepatocytes Culture Device", 16th SICE system integration Division annual conference, 2015, Nagoya, Japan
Patents

 

2014

Journals

 

Invited conferences

 

International conferences with peer reviews

 

National conferences with peer reviews

 

Patents

 

2013 and prior

Journals

 

  2004

  1. E. Leclerc, K.S. Furukawa, F. Miyata, Y. Sakai, T. Ushida, T. Fujii, "Effect on Liver Cells of Stepwise Microstructures Fabricated in a Photosensitive Biodegradable Polymer by Softlithography", Materials Science and Engineering, C-Biomimetic and Supramolecular Systems, Vol. 24, No. 3, pp. 349-354, April 2004.
  2. E. Leclerc, Y. Sakai and T. Fujii, "Microfluidic PDMS (PolyDiMethylSiloxane) Bioreactor for Large-Scale Culture of Hepatocytes", Biotechnology and Progress, Vol. 20, No. 3, pp. 750-755, May-June 2004.
  3. E. Leclerc, K.S. Furukawa, F. Miyata, Y. Sakai, T. Fujii, "Fabrication of Microstructures in Photosensitive Biodegradable Polymers for Tissue Engineering Applications",Biomaterials, Vol. 25, No. 19, pp. 4683-4690, August 2004.
  4. E. Leclerc, Y. Sakai, T. Fujii, "Perfusion Culture of Fetal Human Hepatocytes in Microfluidic-Environments", Biochemical Engineering Journal, Vol. 20, pp. 143-148, 2004.

 

  2003

  1. E. Leclerc, Y. Sakai, and T. Fujii, "Cells culture in a three-dimensional network of PDMS (PolyDiMethylSiloxane) microchannels", Biomedical Microdevices, Vol. 5, No. 2, pp. 109-114, 2003.

 

Conferences

 

  2003

  1. V. Senez, Gonzalo Cabodevila, A. Tixier-Mita, S. Camou, M. Denoual, E. Leclerc, T. Fujii and H. Fujita, "BIOMEMS Activities at LIMMS/CNRS-IIS", The 8th International Micromachine Symposium, Japan, November 14, 2002 (INVITED PAPER).
  2. E. Leclerc, Y. Sakai and T. Fujii, "A Multi-Layer PDMS Microfluidic Device for Tissue Engineering Applications", in Proc. of the 16th IEEE Conference on Micro Electro Mechanical Systems (MEMS'2003), Kyoto, Japan, January, 2003.
  3. E. Leclerc, K.S. Furukawa, F. Miyata, Y. Sakai and T. Fujii, "A Bioreactor for Continuous Perfusion Cell Culture Fabricated with Photosensitive Biodegradable Polymer", in Proc. of the Transducers'2003, Boston, USA, June, 2003.
  4. E. Leclerc, A. Debray, N. Tiercelin, T. Fujii, and H. Fujita, "Silicon based optical scanner using PDMS as torsion springs", in Proc. of the Micro Optical MEMS conference (MOEMS'2003), Hawai, August, 2003.
  5. E. Leclerc, Y. Sakai, T. Fujii, "Fetal Human Hepatocytes and Endotheial Cells co-culture in a microfluidic environment", in Proc. of the 7th International Conference on Miniaturized Chemical and Biochemical Analysis Systems (MICROTAS'2003), Squaw Valley (USA), October, 2003.
  6. N. Tiercelin A. Debray, E. Leclerc, A. Ludwig, E. Quandt, H. Toshiyoshi, T. Fujii and H. Fujita, "Nouveau type de scanner laser 2D pour application automobiles grace aux techniques de micro-usinage" (Text in French), in Proc. of the Journees Scientifiques Francophones 2003 (JSF'2003), Workshop, Tokyo, Japan, November, 2003.

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