Skip to main content

A Novel Microgravity Simulator Applicable for Three-Dimensional Cell Culturing

Microgravity Science and Technology volume 26, pages 77–88 (2014)Cite this 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.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

References

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • Borst, A.G., Van Loon, J.J.: Technology and Developments of the Random Positioning Machine. RPM. Microgravity Sci. Technol. 21, 287–292 (2009)

    Article  Google Scholar 

  • 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 485–476

    Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

  • 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)

    Article  Google Scholar 

  • Cogoli, A., Tschopp, A., Fuchs-Bislin, P.: Cell sensitivity to gravity. Sci. 225(4658), 228–230 (1984)

    Article  Google Scholar 

  • Cogoli-Greuter, M., Pippia, P., Sciola, L., Cogoli, A.: Lymphocytes on sounding rocket flights. J. Gravit. Physiol. 1(1), P90—91 (1994)

    Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  MathSciNet  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • Santini, M.T., Rainaldi, G.: Three-dimensional spheroid model in tumor biology. Pathobiology 67(3), 148–157 (1999)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • Burdick, J.A., Prestwich, G.D.: Hyaluronic acid hydrogels for biomedical applications. Adv. Mater. 23(12), H41–56 (2011). doi: 10.1002/adma.201003963

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Automation, University of Applied Science Northwestern Switzerland, Windisch, Switzerland

    Simon L. Wuest, Roland Anderegg & Jörg Sekler

  2. CC Aerospace Biomedical Science and Technology, Lucerne School of Engineering and Architecture, Seestrasse 41, 6052, Hergiswil, Switzerland

    Simon L. Wuest, Stéphane Richard, Isabelle Walther & Marcel Egli

  3. Institute of Mathematics, University of Zurich, Zürich, Switzerland

    Reinhard Furrer

Authors
  1. Simon L. Wuest
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stéphane Richard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Isabelle Walther
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Reinhard Furrer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Roland Anderegg
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jörg Sekler
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marcel Egli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marcel Egli.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wuest, S.L., Richard, S., Walther, I. et al. A Novel Microgravity Simulator Applicable for Three-Dimensional Cell Culturing. Microgravity Sci. Technol. 26, 77–88 (2014). https://doi.org/10.1007/s12217-014-9364-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12217-014-9364-2

Keywords

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