Taking the 3Rs to a higher level: replacement and reduction of animal testing in life sciences in space research.

Journal: Biotechnology advances
Published Date: Apr 1, 2025

Abstract

Human settlements on the Moon, crewed missions to Mars and space tourism will become a reality in the next few decades. Human presence in space, especially for extended periods of time, will therefore steeply increase. However, despite more than 60 years of spaceflight, the mechanisms underlying the effects of the space environment on human physiology are still not fully understood. Animals, ranging in complexity from flies to monkeys, have played a pioneering role in understanding the (patho)physiological outcome of critical environmental factors in space, in particular altered gravity and cosmic radiation. The use of animals in biomedical research is increasingly being criticized because of ethical reasons and limited human relevance. Driven by the 3Rs concept, calling for replacement, reduction and refinement of animal experimentation, major efforts have been focused in the past decades on the development of alternative methods that fully bypass animal testing or so-called new approach methodologies. These new approach methodologies range from simple monolayer cultures of individual primary or stem cells all up to bioprinted 3D organoids and microfluidic chips that recapitulate the complex cellular architecture of organs. Other approaches applied in life sciences in space research contribute to the reduction of animal experimentation. These include methods to mimic space conditions on Earth, such as microgravity and radiation simulators, as well as tools to support the processing, analysis or application of testing results obtained in life sciences in space research, including systems biology, live-cell, high-content and real-time analysis, high-throughput analysis, artificial intelligence and digital twins. The present paper provides an in-depth overview of such methods to replace or reduce animal testing in life sciences in space research.

Authors

  • Mathieu Vinken
    Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
  • Daniela Grimm
    Department of Microgravity and Translational Regenerative Medicine, Otto-von-Guericke-University, Magdeburg, Germany; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  • Sarah Baatout
    Nuclear Medical Applications Institute, Belgian Nuclear Research Centre, Mol, Belgium; Department of Molecular Biotechnology, Gent University, Gent, Belgium.
  • Bjorn Baselet
    Nuclear Medical Applications Institute, Belgian Nuclear Research Centre, Mol, Belgium.
  • Afshin Beheshti
    Center of Space Biomedicine, McGowan Institute for Regenerative Medicine, and Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Markus Braun
    Host-Pathogen-Interactions, Paul-Ehrlich-Institut, Langen, Germany.
  • Anna Catharina Carstens
    German Space Agency, German Aerospace Center, Bonn, Germany.
  • James A Casaletto
    Blue Marble Space Institute of Science, NASA Ames, Mountain View, USA. james.casaletto@gmail.com.
  • Ben Cools
    Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, Brussels, Belgium; Nuclear Medical Applications Institute, Belgian Nuclear Research Centre, Mol, Belgium.
  • Sylvain V Costes
    NASA Ames Research Center, Moffett Field, CA, USA.
  • Phoebe De Meulemeester
    Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, Brussels, Belgium.
  • Bartu Doruk
    Space Applications Services NV/SA, Sint-Stevens-Woluwe, Belgium; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
  • Sara Eyal
    Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
  • Miguel J S Ferreira
    Space Applications Services NV/SA, Sint-Stevens-Woluwe, Belgium.
  • Silvana Miranda
    Nuclear Medical Applications Institute, Belgian Nuclear Research Centre, Mol, Belgium; Department of Molecular Biotechnology, Gent University, Gent, Belgium.
  • Christiane Hahn
    European Space Agency, Human and Robotic Exploration Programmes, Human Exploration Science team, Noordwijk, the Netherlands.
  • Sinem Helvacıoğlu Akyüz
    Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, Brussels, Belgium.
  • Stefan Herbert
    Space Systems, Airbus Defence and Space, Immenstaad am Bodensee, Germany.
  • Dmitriy Krepkiy
    Office of Special Initiatives, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
  • Yannick Lichterfeld
    Department of Applied Aerospace Biology, Institute of Aerospace Medicine, German Aerospace Center, Cologne, Germany.
  • Christian Liemersdorf
    Department of Applied Aerospace Biology, Institute of Aerospace Medicine, German Aerospace Center, Cologne, Germany.
  • Marcus Krüger
    Department of Thoracic Surgery, Martha-Maria Hospital Halle-Dölau, 06120 Halle, Germany.
  • Shannon Marchal
    Department of Microgravity and Translational Regenerative Medicine, Otto-von-Guericke-University, Magdeburg, Germany.
  • Jette Ritz
    Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, Brussels, Belgium.
  • Theresa Schmakeit
    Department of Applied Aerospace Biology, Institute of Aerospace Medicine, German Aerospace Center, Cologne, Germany.
  • Hilde Stenuit
    Space Applications Services NV/SA, Sint-Stevens-Woluwe, Belgium.
  • Kevin Tabury
    Nuclear Medical Applications Institute, Belgian Nuclear Research Centre, Mol, Belgium.
  • Torsten Trittel
    Department of Microgravity and Translational Regenerative Medicine, Otto-von-Guericke-University, Magdeburg, Germany; Department of Engineering, Brandenburg University of Applied Sciences, Brandenburg an der Havel, Germany.
  • Markus Wehland
    Department of Microgravity and Translational Regenerative Medicine, Otto-von-Guericke-University, Magdeburg, Germany.
  • Yu Shrike Zhang
    Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
  • Karson S Putt
    Institute for Drug Discovery, Purdue University, West Lafayette, IN, USA.
  • Zhong-Yin Zhang
    Institute for Drug Discovery, Purdue University, West Lafayette, IN, USA; Borch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, USA.
  • Danilo A Tagle
    National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, United States.

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