KS5: Role of Gravity and Geomagnetic Field in Flatworm Regeneration (Flatworm Regeneration) - 06.20.18

Overview | Description | Applications | Operations | Results | Publications | Imagery

ISS Science for Everyone

Science Objectives for Everyone
Flatworms regenerate their own cells, replacing them as they age or are damaged. KS5: Role of Gravity and Geomagnetic Field in Flatworm Regeneration (Flatworm Regeneration) studies the cell signaling mechanisms these organisms use while regenerating their tissue in microgravity. Results provide insight into how gravity affects tissue regeneration and the rebuilding of damaged organs and nerves, which is important for understanding how wounds heal in space.
Science Results for Everyone
Off with their heads! Or tails. Flatworms sent to space with their heads or tails removed did not differ in size after regeneration from those kept on the ground. Researchers saw unusual characteristics in the space flatworms after regeneration, however – including an extremely rare double-headed phenotype, which repeated after subsequent rounds of regeneration back on Earth. Analysis detected chemical differences in the water that reflect flatworm metabolism and secretion being altered in space. Additional analysis 20 months later showed significant differences in the amount of time the space worms and ground controls spent in the dark, a measure of behavior, with space flatworms being more varied in their preference for light levels. Also different was the microbiota – bacteria that live on the worms.

The following content was provided by Twyman S. Clements, M.S., and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom: Flatworm Regeneration

Principal Investigator(s)
Michael Levin, Ph.D., Tufts University, Medford, MA, United States

Twyman S. Clements, M.S., Space Tango, Inc., Lexington, KY, United States

Center for the Advancement of Science in Space (CASIS), Melbourne, FL, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
National Laboratory (NL)

Research Benefits
Earth Benefits

ISS Expedition Duration
September 2014 - March 2015

Expeditions Assigned

Previous Missions
Information Pending

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Experiment Description

Research Overview

  • Sending human beings to space represents a set of challenges and, importantly, a set of opportunities for biology, biomedicine, and technology.
  • The challenges consist of understanding how loss of normal cues such as gravity and geomagnetic field impact basic cell function and large-scale processes such as tissue regeneration.
  • These same factors represent remarkable opportunities for advances that impact not only space exploration but technology for everyone on Earth.  Research in microgravity and null geomagnetic field environments enables learning about these important factors in the regulation of cell behavior.
  • Investigating the mechanisms by which regenerative organisms detect and repair complex organ structures enables the development of robust technologies that reconfigure their energy dynamics and material composition to repair damage and keep functioning when the unexpected occurs far from a terrestrial repair facility.

Advances in the regenerative process will have transformative implications for regenerative medicine as well as design of flexible, robust robotic and communication systems. In KS5: Role of Gravity and Geomagnetic Field in Flatworm Regeneration (Flatworm Regeneration), it is proposed to expose planarians to the microgravity environment to understand the role of gravity in their amazing healing abilities. The experiment includes intact control worms, and worms with their heads or tails amputated, placed in sealed spring water vials before sending these into space immediately after amputation. The regeneration patterns are analyzed (via morphological and molecular-genetic methods) in the lab on Earth upon their return.

It is important to understand how living tissues use physical forces to control pattern formation., A specific hypothesis about the role of gravity and the geomagnetic field in the pathways that regulate complex tissue patterning and wound healing is made once it is determined what aspects of morphogenesis are disrupted by microgravity and loss of the geomagnetic field.

For measuring and scoring the molecular difference in the flatworms, in situ hybridization or immunohistochemistry is used.  The same criteria as used in the hundreds of published papers in the planarian model system is utilized, which is the difference between control and experimental patterns should be bigger than the difference observed within the group of approximately 20 controls. Immunofluorescence and in situ hybridization signal is not usually quantified - the expression of transcripts or proteins in inappropriate locations (e.g., a head marker expressed in a tail wound) is quite obvious - a qualitative, not quantitative, difference.

Progress into the basic mechanisms of embryonic development and complex organ repair/regeneration advances space exploration. Experiments conducted in the unique environment of space enrich understanding of biophysical mechanisms that underlie complex pattern formation. In particular, the role of bioelectrical signals in this process needs to be understood, as these signals are an especially powerful means of cell regulation that underlie information processing in all cell groups.

The objective of Flatworm Regeneration is to understand the first step in “mapping’ the mechanisms of how an organism determines the placement of damage and how it instructs the “leading edge” to grow the particular area or appendage that has been damaged. This mapping may lead to more effective treatments in conditioning injuries for regrowth by coaxing the damaged area into appropriate growth. Additionally the mapping could be used as the basis for algorithms of self-replicating or repairing robots which themselves have boundless uses.

The growth of the flatworm is analyzed morphologically (looking at anatomical markers such as shape, size, and proportion of the different regenerated organs) and, any differences from control animals are noted, with further analysis using molecular genetics (for spatial expression profiles of genes known to control regenerative patterning) to understand the mechanism by which the changes in regenerative shape occurred.  Molecular analysis will include in situ hybridization and immunehisto-chemistry for markers of head blastema, tail blastema, innervation, eye tissue, neoblasts (stem cells), apoptosis (programmed cell death), and a set of ion channels and pumps known to be important for normal patterning.

This is the first, and unique, effort to understand these two factors in regenerative response of a complex neural organ system – really crucial to begin to determine how physical forces impact on the molecular genetic pathways that rebuild and repair living structures. The data generates mechanistic hypotheses that can be further tested to understand both the dangers of this kind of environment and, more importantly, to learn to exploit these physical forces to increase regenerative repair. The results obtained in this experiment will become the basis for next phase of the Exomedicine research in the regenerative medicine area.

For the Regeneration investigation, the flatworms are contained within sealed test tubes or vials which themselves are held in two BRIC-100 VC canisters hardware made by QinetiQ. These samples are kept at a sub-optimal temperature for growth (preferably +10°C-14°C) before and during flight to the International Space Station (ISS). This approach allows as much regeneration to happen as possible in the microgravity environment.  A data logger is also included in the BRIC to keep track of temperature, pressure, magnetic field, and vibration over the duration of the experiment.  The flatworms are shipped alive pre-flight and returned to the investigator alive post-flight.

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Space Applications
Future long-duration space missions will not have easy access to Earth-based services, so an improved ability to fix equipment would be beneficial. Understanding the cellular mechanisms behind a flatworm’s ability to regrow its own tissue provides new insight into this unique healing method. New technologies based on these abilities could reconfigure their own components and energy use, repairing damage to themselves while still being used. Self-healing and self-repair can reduce risks when an emergency happens.

Earth Applications
Regenerative medicine can help patients suffering from a wide range of injuries and physical impairments, by replacing, repairing or re-growing damaged tissue. Regenerative medicine can be used to treat spinal cord injury, heart failure, insulin-dependent diabetes, and degenerative brain diseases such as Parkinson’s disease, benefiting millions of people on Earth. By focusing on the cellular level, scientists can greater understand the mechanisms behind regenerative ability. Cell-based products, such as cellular matrix powder, could also be used to aid in regenerating lost tissue, even lost fingers or limbs.

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Operational Requirements and Protocols
The two sample canisters remain sealed for duration of the flight. They are unpowered, and require +12°C for ascent and descent.

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Decadal Survey Recommendations

Information Pending

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Results/More Information

This study examined the regeneration of planarian flatworms in microgravity and loss of geomagnetic field. The heads and tails of fifteen flatworms were removed and then launched into space to regenerate on the International Space Station (ISS) for 5 weeks. A control group of flatworms remained on earth for later comparison against the experimental space travel-exposed group. Samples were analyzed upon return from the ISS and 20 months later. Relative to ground controls, results showed that space flatworms did not differ in size but exhibited several unusual characteristics. For example, one flatworm fragment out of 15 regenerated with an extremely rare double-headed phenotype. Investigators additionally examined the chemical composition of the water flatworms were living in (i.e., ions and proteins), finding differences in the water – which could reflect to changes in metabolism or secretion of the flatworms. In the post 20-month analysis, researchers found significant differences between the groups with respect to how much time the flatworms spent in the dark (a measure of behavioral preferences); moreover, space flatworms exhibited more variability in their preference for light levels. Another difference between space-exposed and Earth control worms was the profile of bacteria that live on the planaria. The planaria flatworm is a prime model for research in stem cell biology and it is ideal for exploratory science on the ISS.

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Results Publications

    Morokuma J, Durant FR, Williams KB, Finkelstein JM, Blackiston DJ, Clements TS, Reed DW, Roberts MS, Jain M, Kimel K, Trauger SA, Wolfe BE, Levin M.  Planarian regeneration in space: persistent anatomical, behavioral, and bacteriological changes induced by space travel. Regeneration. 2017 April 1; epub. DOI: 10.1002/reg2.79.

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Ground Based Results Publications

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ISS Patents

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Related Publications

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Related Websites
The Levin Lab
Kentucky Space

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image Representative images of animals with single, bipolar, triple, and quadruple heads for the KS5: Role of Gravity and Geomagnetic Field in Flatworm Regeneration (Flatworm Regeneration) investigation. Image courtesy of Dr. Michael Levin, Tufts University.
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BRIC-100 VC Canister Hardware for the KS5: Role of Gravity and Geomagnetic Field in Flatworm Regeneration (Flatworm Regeneration) investigation. Image courtesy of QinetiQ.

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image Sample test tubes utilized in the KS5: Role of Gravity and Geomagnetic Field in Flatworm Regeneration (Flatworm Regeneration) investigation.
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