Microgravity Science and Technology

, Volume 26, Issue 2, pp 77–88 | Cite as

A Novel Microgravity Simulator Applicable for Three-Dimensional Cell Culturing

  • Simon L. Wuest
  • Stéphane Richard
  • Isabelle Walther
  • Reinhard Furrer
  • Roland Anderegg
  • Jörg Sekler
  • Marcel Egli
Original Article

Abstract

Random Positioning Machines (RPM) were introduced decades ago to simulate microgravity. Since then numerous experiments have been carried out to study its influence on biological samples. The machine is valued by the scientific community involved in space relevant topics as an excellent experimental tool to conduct pre-studies, for example, before sending samples into space. We have developed a novel version of the traditional RPM to broaden its operative range. This novel version has now become interesting to researchers who are working in the field of tissue engineering, particularly those interested in alternative methods for three-dimensional (3D) cell culturing. The main modifications concern the cell culture condition and the algorithm that controls the movement of the frames for the nullification of gravity. An incubator was integrated into the inner frame of the RPM allowing precise control over the cell culture environment. Furthermore, several feed-throughs now allow a permanent supply of gas like CO 2. All these modifications substantially improve conditions to culture cells; furthermore, the rewritten software responsible for controlling the movement of the frames enhances the quality of the generated microgravity. Cell culture experiments were carried out with human lymphocytes on the novel RPM model to compare the obtained response to the results gathered on an older well-established RPM as well as to data from space flights. The overall outcome of the tests validates this novel RPM for cell cultivation under simulated microgravity conditions.

Keywords

Random Positioning Machine Microgravity Tissue engineering 3D cell cuturing Kinematic acceleration 

References

  1. Anders, M., Hansen, R., Ding, R.X., Rauen, K.A., Bissell, M.J., Korn, W.M.: Disruption of 3D tissue integrity facilitates adenovirus infection by deregulating the coxsackievirus and adenovirus receptor. Proc. Natl. Acad. Sci. U. S. A. 100(4), 1943–1948 (2003)CrossRefGoogle Scholar
  2. Barrila, J., Radtke, A.L., Crabbe, A., Sarker, S.F., Herbst-Kralovetz, M.M., Ott, C.M., Nickerson, C.A.: Organotypic 3D cell culture models: using the rotating wall vessel to study host-pathogen interactions. Nat. Rev. Microbiol. 8(11), 791–801 (2010)CrossRefGoogle Scholar
  3. Borst, A.G., Van Loon, J.J.: Technology and Developments of the Random Positioning Machine. RPM. Microgravity Sci. Technol. 21, 287–292 (2009)CrossRefGoogle Scholar
  4. Butcher, J.T., Nerem, R.M.: Porcine aortic valve interstitial cells in three-dimensional culture: comparison of phenotype with aortic smooth muscle cells. J. Heart Valve Dis. 13(3), 478–485 (2004). discussion 485–476Google Scholar
  5. Cadee, J.A., van Luyn, M.J., Brouwer, L.A., Plantinga, J.A., van Wachem, P.B, de Groot, C.J., den Otter, W., Hennink, W.E.: In vivo biocompatibility of dextran-based hydrogels. J. Biomed. Mater. Res. 50(3), 397–404 (2000)CrossRefGoogle Scholar
  6. Cascone, M.G., Barbani, N., Cristallini, C., Giusti, P., Ciardelli, G., Lazzeri, L.: Bioartificial polymeric materials based on polysaccharides. J. Biomater. Sci. Polym. Ed. 12(3) (2001)Google Scholar
  7. Chang, T.T., Walther, I., Li, C.F., Boonyaratanakornkit, J., Galleri, G., Meloni, M.A., Pippia, P., Cogoli, A., Hughes-Fulford, M.: The Rel/NF-kappaB pathway and transcription of immediate early genes in T cell activation are inhibited by microgravity. J. Leukoc. Biol. 92(6), 1133–1145 (2012)CrossRefGoogle Scholar
  8. Cogoli, A., Tschopp, A., Fuchs-Bislin, P.: Cell sensitivity to gravity. Sci. 225(4658), 228–230 (1984)CrossRefGoogle Scholar
  9. Cogoli-Greuter, M., Pippia, P., Sciola, L., Cogoli, A.: Lymphocytes on sounding rocket flights. J. Gravit. Physiol. 1(1), P90—91 (1994)Google Scholar
  10. Cogoli-Greuter, M., Meloni, M.A., Sciola, L., Spano, A., Pippia, P., Monaco, G., Cogoli, A.: Movements and interactions of leukocytes in microgravity. J. Biotechnol. 47(2–3), 279–287 (1996)CrossRefGoogle Scholar
  11. Eyrich, D., Brandl, F., Appel, B., Wiese, H., Maier, G., Wenzel, M., Staudenmaier, R., Goepferich, A., Blunk, T.: Long-term stable fibrin gels for cartilage engineering. Biomater. 28(1), 55–65 (2007)CrossRefGoogle Scholar
  12. Friedrich, J., Seidel, C., Ebner, R., Kunz-Schughart, L.A.: Spheroid-based drug screen: considerations and practical approach. Nat. Protoc. 4(3), 309–324 (2009)CrossRefGoogle Scholar
  13. Gmunder, F.K., Kiess, M., Sonnefeld, G., Lee, J., Cogoli, A.: A ground-based model to study the effects of weightlessness on lymphocytes. Biol. Cell 70(1–2), 33–38 (1990)CrossRefGoogle Scholar
  14. Ho, S.T., Cool, S.M., Hui, J.H., Hutmacher, D.W.: The influence of fibrin based hydrogels on the chondrogenic differentiation of human bone marrow stromal cells. Biomater. 31(1), 38–47 (2010)CrossRefGoogle Scholar
  15. Hughes, C.S., Postovit, L.M., Lajoie, G.A.: Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics 10(9), 1886–1890 (2010)CrossRefGoogle Scholar
  16. Ivascu, A., Kubbies, M.: Rapid generation of single-tumor spheroids for high-throughput cell function and toxicity analysis. J. Biomol. Screen. 11(8), 922–932 (2006)CrossRefGoogle Scholar
  17. Kleinman, H.K., McGarvey, M.L., Liotta, L.A., Robey, P.G., Tryggvason, K., Martin, G.R.: Isolation and characterization of type IV procollagen, laminin, and heparan sulfate proteoglycan from the EHS sarcoma. Biochem. 21(24), 6188–6193 (1982)CrossRefGoogle Scholar
  18. Kleinman, H.K., McGarvey, M.L., Hassell, J.R., Star, V.L., Cannon, F.B., Laurie, G.W., Martin, G.R.: Basement membrane complexes with biological activity. Biochem. 25(2), 312–318 (1986)CrossRefGoogle Scholar
  19. Kraft, T.F., van Loon, J.J., Kiss, J.Z.: Plastid position in Arabidopsis columella cells is similar in microgravity and on a random-positioning machine. Planta 211(3), 415–422 (2000)CrossRefGoogle Scholar
  20. Lin, R.Z., Chang, H.Y.: Recent advances in three-dimensional multicellular spheroid culture for biomedical research. Biotechnol. J. 3(9–10), 1172–1184 (2008)MathSciNetCrossRefGoogle Scholar
  21. Masters, K.S., Shah, D.N., Leinwand, L.A., Anseth, K.S.: Crosslinked hyaluronan scaffolds as a biologically active carrier for valvular interstitial cells. Biomater. 26(15), 2517–2525 (2005)CrossRefGoogle Scholar
  22. Pietsch, J., Sickmann, A., Weber, G., Bauer, J., Egli, M., Wildgruber, R., Infanger, M., Grimm, D.: A proteomic approach to analysing spheroid formation of two human thyroid cell lines cultured on a random positioning machine. Proteomics 11(10), 2095–2104 (2011)CrossRefGoogle Scholar
  23. Pippia, P., Sciola, L., Cogoli-Greuter, M., Meloni, M.A., Spano, A., Cogoli, A.: Activation signals of T lymphocytes in microgravity. J. Biotechnol. 47(2–3), 215–222 (1996)CrossRefGoogle Scholar
  24. Santini, M.T., Rainaldi, G.: Three-dimensional spheroid model in tumor biology. Pathobiology 67(3), 148–157 (1999)CrossRefGoogle Scholar
  25. Shaw, K.R., Wrobel, C.N., Brugge, J.S.: Use of three-dimensional basement membrane cultures to model oncogene-induced changes in mammary epithelial morphogenesis. J. Mammary Gland Biol. Neoplasia 9(4), 297–310 (2004)CrossRefGoogle Scholar
  26. van Loon, J.J.: Some history and use of the random positioning machine, RPM, in gravity related research. Adv. Space Res. 39, 1161–1165 (2007)CrossRefGoogle Scholar
  27. Weaver, V.M., Petersen, O.W., Wang, F., Larabell, C.A., Briand, P., Damsky, C., Bissell, M.J.: Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies. J. Cell Biol. 137(1), 231–245 (1997)CrossRefGoogle Scholar
  28. Wenger, A., Stahl, A., Weber, H., Finkenzeller, G., Augustin, H.G, Stark, G.B., Kneser, U.: Modulation of In Vitro Angiogenesis in a Three-Dimensional Spheroidal Coculture Model for Bone Tissue Engineering. Tissue Eng. 10(9–10), 1536–1547 (2004)CrossRefGoogle Scholar
  29. Wenger, A., Kowalewski, N., Stahl, A., Mehlhorn, A.T., Schmal, H., Stark, G.B., Finkenzeller, G.: Development and Characterization of a Spheroidal Coculture Model of Endothelial Cells and Fibroblasts for Improving Angiogenesis in Tissue Engineering. Cells Tissues Organs 181(2), 80–88 (2005)CrossRefGoogle Scholar
  30. Wolf, K., Mazo, I., Leung, H., Engelke, K., von Andrian, U.H., Deryugina, E.I., Strongin, A.Y., Brocker, E.B., Friedl, P.: Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis. J. Cell Biol. 160(2), 267–277 (2003)CrossRefGoogle Scholar
  31. Burdick, J.A., Prestwich, G.D.: Hyaluronic acid hydrogels for biomedical applications. Adv. Mater. 23(12), H41–56 (2011). doi: 10.1002/adma.201003963 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Simon L. Wuest
    • 1
    • 2
  • Stéphane Richard
    • 2
  • Isabelle Walther
    • 2
  • Reinhard Furrer
    • 3
  • Roland Anderegg
    • 1
  • Jörg Sekler
    • 1
  • Marcel Egli
    • 2
  1. 1.Institute for AutomationUniversity of Applied Science Northwestern SwitzerlandWindischSwitzerland
  2. 2.CC Aerospace Biomedical Science and TechnologyLucerne School of Engineering and ArchitectureHergiswilSwitzerland
  3. 3.Institute of MathematicsUniversity of ZurichZürichSwitzerland

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