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Microgravity Environment - New Organ Alliance

Microgravity Environment

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MICROGRAVITY ​
TECHNOLOGY TOPIC

In orbit around the Earth, astronauts experience a free fall environment where the pull of gravity is not very strong. This is microgravity and one of several unique facets of the ISS National Laboratory that enables scientific discovery and catalyzes medical innovation to benefit life on Earth. 

Microgravity induces a vast array of changes in organisms ranging from individual cells to humans and their associated microbiomes, including alterations in gene expression and the 3-dimensional aggregation of cells into tissues and organs in the near absence of mechanical loading.


Cellular proliferation, differentiation and aggregation into tissue-like architectures in microgravity is especially beneficial to understanding the bioengineering of tissues and organs because of the ability to culture and observe cells ex vivo without sedimentation. In vivo, microgravity induces changes to organisms that mimic human diseases on Earth associated with aging, immune dysfunction, inflammation response, and musculoskeletal defects.


In space, several changes take place in cells, including changes in cell signaling (the way cells share information), cell aggregation (the physical contact between cells leading to their 3D structural organization into tissues), and matrix deposition. Microgravity also profoundly changes the physics of fluid movement and the way nanoparticles and cells combine. These cellular and physical changes provide opportunities for discoveries, impossible on Earth, that may help to end the organ shortage.

The ISS-NL Opportunity

In 2005, Congress designated the U.S. portion of the International Space Station as the nation’s newest national laboratory to maximize its use for improving life on Earth, promoting collaboration among diverse users, and advancing STEM education.  


This unique laboratory environment is available to commercial companies, other U.S. government agencies, and by academic and private institutions, providing access to the permanent microgravity setting, vantage point in low Earth orbit, and varied environments of space.


Advances in stem cell biology, the development of tissue chips, and 3D bioprinting on Earth are helping to accelerate drug discovery and bring the possibility of bioengineering whole organs for transplantation closer to reality.  These advances are being further accelerated using the unique microgravity environment onboard the ISS.


Results from research conducted in microgravity have the potential to contribute to advanced understanding and potential solutions for some of the most significant challenges in the field of regenerative medicine. 

Challenge & Sub-Challenge Impact Statements

How does microgravity influence cell differentiation?

Understanding what makes a stem cell a stem cell – ‘stemness’ or the unique properties that allow for cells to grow and differentiate into various tissue types - is a key question in the field of regenerative medicine.  Additionally, producing therapeutic levels of cells has to date proven costly using conventional methods of cell culture and expansion. Of particular interest is the finding that microgravity increases proliferation and delays differentiation in stem cells (See references 1-11 below).  Understanding ‘stemness’ and ways to produce adequate treatment volumes of therapeutic cells more cost efficiently could advance  the field of regenerative medicine and have a significant impact for patients here on Earth.

Related Challenge Topics: Cell Sourcing

Related Sub-Challenge Topics: Improved Understanding of Stem Cell Differentiation Protocols and Markers; Identification of Reliable and Available Growth Factors

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How does microgravity affect proper integration of cell types and tissue networks during organ development?

For example, how matrix is deposited by the cell to form a tissue, how cells interact within the matrix, and how the complex vasculature of tissue is altered or contributes during tissue development in microgravity are all key questions to advancing understanding where microgravity provides opportunities for new learnings that support future development of tissues and functional organs.  CASIS is looking forward to working with the NASA Vascular Tissue Challenge Centennial prize winners to advance understanding of ground-based systems that are developed in this challenge and conducting research in microgravity onboard the International Space Station through the Innovations in Space Award.

Related Challenge Topics: Integration, Vascularization 

Related Sub-Challenge Topics: Understand the developmental timeline for vascularization of tissues

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How does cell organization in microgravity differ from that which occurs naturally on Earth?

Organoids have gained attention for their ability to “mimic” developmental processes, so can these organoids be used as a surrogate model to better understand how organ development would happen in microgravity? For example, if a neural or cardiac organoid (composed of the various cell types of the brain or heart, respectively) was allowed to self-aggregate in microgravity, how would that aggregation differ from that which occurs on Earth? In other words, is gravity a critical cue for proper cellular organization during neural or cardiac development? Research on Tissue Chips in Space through a collaboration with NIH and CASIS is evaluating 5 different tissue types including lung, brain, cartilage/bone, bone marrow and kidney provide opportunities to contribute learnings to many of the specific tissue related challenges and sub-challenges. Selection of projects for an additional collaboration between NIH and CASIS for Tissue Chips in Space 2.0 is underway. Additionally, CASIS will be evaluating bone, smooth muscle, and nerve will be studied via tissue-on-chip systems that are under development for research in microgravity.

Related Challenge Topics: Cell Mapping 

Related Sub-Challenge Topics: Improved Understanding of Mechanical Loading Environment​ 

How can microgravity support the development of other enabling technologies?

Precision engineering and design requirements of systems used to support cell culture, tissue chip research, and 3D bioprinting in microgravity provide opportunities for learning that can be directly translated to improving ground-based systems.  Additionally, CASIS and NSF have initiated a collaboration for Tissue Engineering on The International Space Station to Benefit Life on Earth.  Specifically, this initiative addresses:


  • Development of validated models (living or computational) of normal and pathological tissues and organ systems that can support development and testing of medical interventions
  • Design of systems that integrate living and non-living components for improved diagnosis, monitoring, and treatment of disease or injury
  • Advanced biomanufacturing of three-dimensional tissues and organs
  • Design and subsequent application of technologies and tools to investigate fundamental physiological and pathophysiological processes


Additionally, several groups are working on improved cryopreservation methods that will enable long-term storage and transport of tissues and organs created on station.

Related Enabling Technologies: Improved Bioreactors, Improved Bioprinters, Improved Hydrogels, Improved Bio-degradable Scaffolds, Tissue Preservation

  • Baio J., A. F. Martinez, L. Bailey, N. Hasaniya, M. J. Pecaut, and M. Kearns-Jonker (2018) Spaceflight Activates Protein Kinase C Alpha Signaling and Modifies the Developmental Stage of Human Neonatal Cardiovascular Progenitor Cells. Stem Cells and Development. February 2018, ahead of print. https://doi.org/10.1089/scd.2017.0263
  • Bauer, J., M. Bussen, P. Wise, M. Wehland, S. Schneider and D. Grimm (2016) Searching the literature for proteins facilitates the identification of biological processes, if advanced methods of analysis are linked: a case study on microgravity-caused changes in cells. Expert Review of Proteomics. 13(7):697-705. doi: 10.1080/14789450.2016.1197775.
  • Blaber, E. A., H. Finkelstein, N. Dvorochkin, K. Y. Sato, R. Yousuf, B. P. Burns, R. K. Globus, and E. A. Almeida (2015) Microgravity Reduces the Differentiation and Regenerative Potential of Embryonic Stem Cells. Stem Cells Dev 24(22):2605-21. doi: 10.1089/scd.2015.0218. Epub 2015 Oct 22.
  • Costantini, D. V. Cardinale, L. Casadei, G. Carpino, L. Nevi, S. Di Matteo, A. M. Lustri, S. Safarikia, F. Melandro, P. Berloco, C. Manetti, and D. Alvaro. (2017) Microgravity maintains stemness and enhance glycolytic metabolism in human hepatic and biliary tree stem/progenitor cells. Digestive and Liver Disease, 49(1): e14. http://www.dldjournalonline.com/article/S1590-8658(17)30034-8/pdf
  • Fuentes, T. I., N. Appleby, M. Raya, L. Bailey, N. Hasaniya, L. Stodieck, and M. Kearns-Jonker (2015) Simulated Microgravity Exerts an Age-Dependent Effect on the Differentiation of Cardiovascular Progenitors Isolated from the Human Heart. PLOS One 10(7): e0132378. https://doi.org/10.1371/journal.pone.0132378
  • Grimm, D., M. Wehland, J. Pietsch, G. Aleshcheva, P. Wise, J. van Loon, C. Ulbrich, N. E. Magnusson, M. Infanger, and J. Bauer. (2014) Tissue Engineering Part B: Reviews. 20(6): 555-566. https://doi.org/10.1089/ten.teb.2013.0704
  • Han, J., and J. Dai (2016) Microgravity may help future organ/tissue manufacture. Sci China Life Sci 59: 850–853. doi:10.1007/s11427-016-5079-5
  • Nickerson C.A., Mark Ott C. (2016) Biomedical Advances in Three Dimensions: An Overview of Human Cellular Studies in Space and Spaceflight Analogues. In: Nickerson C., Pellis N., Ott C. (eds) Effect of Spaceflight and Spaceflight Analogue Culture on Human and Microbial Cells. Springer, New York, NY.
  • Rajneesh J., Q. Wu, M. Singh, M. K. Preininger, P. Han, G. Ding, H. C. Cho, H. Jo, K. O. Maher, M. B. Wagner, and C. Xu. (2016) Simulated Microgravity and 3D Culture Enhance Induction, Viability, Proliferation and Differentiation of Cardiac Progenitors from Human Pluripotent Stem Cells. Scientific Reports 6: 30956. doi:10.1038/srep30956
  • Silvano, M., et al. (2015) Consequences of Simulated Microgravity in Neural Stem Cells: Biological Effects and Metabolic Response. J Stem Cell Res Ther 5:289. doi:10.4172/2157-7633.1000289
  • Yuge, L., T. Kajiume, H. Tahara, Y. Kawahara, C. Umeda, R. Yoshimoto, S-L Wu, K. Yamaoka, M. Asashima, K. Kataoka, and T. Ide (2007) Stem Cells and Development 15(6): 921-929. https://doi.org/10.1089/scd.2006.15.921

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