Organ-on-Chip Technologies: the quest for a real trustful biological model
Organ chip technology: from systems biology to societal issues
Milan - Program:
Thursday 22nd (9:00-17:30, 17:30-18:30 poster session) – Friday 23rd (9:00-15:00) of November 2018
Marta Bertolaso (Università Campus Bio-Medico, Roma)
Silvia Caianiello (CNR, Napoli)
Lilia Alberghina (SYSBIO/ISBE.IT – Centre of Systems Biology, University of Milano-Bicocca, Milano)
Andrea Pensotti (Università Campus Bio-Medico di Roma)
The need for a more effective biological experimental setup to model inter-level regulatory processes is pushing both biomedical sciences and technology toward new goals. In concrete, the merging of cell biology, micro fabrication techniques and microfluidics has fostered the development of Organs-on-Chip (OoC), which recapitulate the tissue-tissue interfaces that build the key functional units of single organs, and even Bodies-on-chip, which recapitulate the functional interaction among different organs. In the coming future we will be able to better model metabolic and regulatory dynamics, overcoming traditional limits of one or two-dimensional analysis (e.g. petri dish analysis). The dynamic phenotypic heterogeneity at different levels of the biological organization (from cell to tissue to organism) will no be further a problem, but a fundamental source of a deeper understanding of the biological complexity. This breakthrough will be particularly evident for cancer, autoimmune and neurodegenerative diseases.
Endowed with multiple sensing and actuating devices, OoC technology allows in fact both the high-throughput real-time measure of multiple crucial parameters independently from each other, and the mimicking of the physiological and pathological dynamics of the organ or organ system. For these reasons OoC have been hailed as experimental systems for advancing Systems Biology to 3d and even 4d dimensionality. They are finding crucial applications both for basic biological research (physiology, embryogenesis and developmental biology, cell differentiation and tissue organization) and for biomedicine (complex disease modeling, drug development and toxicity assays, individualized and personalized medicine).
Systems Biology approach relies on the iterative cycling of high-throughput technologies, ‘wet’ experimental research, and ‘dry’ modeling strategies. Through the OoC technologies, embodied in vitro models are available for further testing. That is, refining them in a realistic 3d environment it is possible to mimic in real time the dynamics of the system under study and under specific physiological and pathological conditions.
That approach led to the development of partial reality-fitting explanatory and experimental models.
For this reason several issues and challenges of modern research are still partially clear. Cancer, neurodegenerative diseases, auto-immune diseases are some examples of research challenges that may benefit from this new approach.
Furthermore the cost-impact of this research programs will benefit of more accurate internal validation processes as well as external ones, i.e. the possibility to export and apply models to different clinical practice fields, reducing the risk of errors in understanding and for treatments.
Conference aims and scope
The present conference aims to promote an interdisciplinary evaluation on the promises and implications of this new technology both for science and for society at large.
- State of the art – Present ongoing applications of OoC to
a. basic systems biology research (homeostasis, cell differentiation and tissue organization);
b. biomedical research (complex diseases systems biology modeling, , individualized medicine by employment of ex vivo cells, drug screening and toxicity assays)
- Technological challenges – issues related to
c. effective miniaturization as well as automation of the whole process;
d. real-time temporal control methods;
f. prospective merging of organoid and organ-on-chip technology
- Theoretical and societal implications
g. Theoretical and epistemological issues: OoC as systems biology experimental models, integration of 3d (in particular biomechanical factors) and 4d dimensions (modes and limits of functional reduction, modeling and integration of multiscale processes and regulatory levels).
h. Societal issues: evaluation both of prospective societal advantages (democratic accessibility of sophisticated testing offering cost reduction; reduction of animal testing) and concerns (legal and bioethical implications of externalization of biological identity into portable devices).
- Case studies: TBC depending on the final agenda
- Donald Ingber (tensegrity)
- J Knoblich Vienna (minibrain organoids)
- Eric B. Winsberg (theoretical/societal issues)
- Marco Vanoni, Sysbio (Systems Biology and organs on a chip)
- Matteo Moretti, Cell Tissue lab (microfluidic organ on chip, ex. muscle tissue, breast cancer metastasis)
- (also from IMBA, Vienna) Bon-Kyoung Koo (Koo Lab in which: mouse and patient-derived 3D organoids as a screening platform to identify new players regulating adult stem cells (INTESTINAL & CARDIOVASCULAR organoid cultures)
- Boudewijn Burgering, UMC Utrecht, center for molecular medicine, section molecular cancer research, Telephone number: + 31 88 7568918 /8988-mail address: B.M.T.Burgering@umcutrecht.nl (study of metabolic regulation in cancer and differentiation: interaction between protein signaling networks with that of metabolic pathways with small intestinal organoid culture systems)
- Alberto Rainer et al, Campus BioMedico, (con Businaro?)
- Francesco Pampaloni, Buchmann Institute Frankfurt (Germany), (working on: Phenotypic screening of autophagy modulating drugs in a three dimensional human brain cancer model, but co-author of review on the transition from 2D to microengineered 3D in vitro models)
- Luca Businaro et al., Institute for Photonics and Nanotechnologies IFN, CNR Rome (2017 Organs on chip approach: a tool to evaluate cancer -immune cells interactions) (paper also with Italians working in France and München, Germany…)
- Jan G. Hengstler et al…, Head of Dpt Systems Toxicology di Ifado Leibniz Research Centre for working environment and human factors (che hanno un EU-Project in Toxicity Testing and Risk Assessment for the 21century), (2015: 3D spherical microtissues and microfluidic technology for multi-tissue experiments and analysis) – (al are also from Switzerland and KU Leuven, Research Group of Functional Genomics and Proteomics, Naamsestraat 59, 3000 Leuven, Belgium: Bart Landuyt (innovation manager) tel. +32 16 32 37 54 firstname.lastname@example.org Kurt Boonen)
- Jochen Kieninger, Andreas Weltlin, Hubert Flamm, Gerald A Urban, Dpt of Microsystems Engineering -. IMTEK – University of Freiburg, Germany E-mail: email@example.com; Tel: +49 761 203 726 (Microsensor systems for cell metabolism – from 2d culture to organ-on-chip 2018)
- Knoblich IMBA https://www.imba.oeaw.ac.at Cerebral organoids for modeling interactions between brain regions 2017
- Marta Bertolaso (UCBM)
- Silvia Caianiello (CNR)
- Sarah Green and/or Tarja Knuuttila, University of Helsinki (University of Copenhagen)
- John Dupré (Exeter)
- Mariachiara Tallacchini, Cattolica di Piacenza
- Carlo Casonato, University of Trento (Biolaw)
- Evt for bioethical issues: Bernadette Bensaude-Vincent (Paris, University Paris 1 Pantheon) OR Alfred Nordmann (TU Darmstadt, Germany) OR Timothy Lenoir (UC Davis USA)