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An in Vitro Study on Tissue Repair: Impact of Unloading on Cells Involved in the Remodelling Phase

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Abstract

The number of astronauts involved in long-lasting missions and extra-vehicular activities is going to increase in the future. Consequently, the chance of injury due to traumatic events or unexpected emergency surgery will also increase and medical evacuation times to earth will be prolonged. Hence, the need to address requirements for surgery and trauma care in non terrestrial environments will be a priority. Tissue repair in weightlessness should therefore be regarded as a major issue not enough studied to date. Wound healing is a complex multi-step process, crucial to the survival of the organism. It starts with an inflammatory phase followed by a remodelling phase. During repair, the extracellular matrix (ECM) is sequentially remodelled by the concerted action of different cell types, in order to rebuild a functional tissue. The available literature concerning wound healing with mechanical unloading presents controversial results. However, many studies indicate impairment of the healing processes. Here we present a study on the behaviour of cells involved in the remodelling phase of repair, e.g. fibroblasts and endothelial cells, in response to microgravity (μg). In particular, their adhesion/migration, cytoskeleton organization, production of ECM molecules and receptors have been investigated. Cell response to pulsed Nd:YAG laser irradiation has also been investigated in order to evaluate the possibility to use laser irradiation for counteracting the effect of μg on wound healing. In μg, we observed alterations in production/assembling of ECM molecules. Increased fibronectin (FN) and laminin (LM) could be the cause for impaired ECM rebuilding and altered cell adhesion/migration. Treatment with Nd:YAG laser pulses induced organized fibrillogenesis and favoured endothelial cell spreading and monolayer formation. These findings open the way for a better understanding of tissue repair mechanisms in space and future clinical applications on earth.

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References

  • Basile, V., Romano, G., Fusi, F., Monici, M.: Comparison between the effects of hypergravity and photomechanical stress on cells producing ECM. Microgravity Sci. Technol. 21, 151–157 (2009) doi:10.1007/s12217-008-9068-6

    Article  Google Scholar 

  • Beck, K., Hunter, I., Engel, J.: Structure and function of laminin: anatomy of a multidomain glycoprotein. FASEB J. 4(2), 148–160 (1990)

    Google Scholar 

  • Campbell, M.R., Kirkpatrick, A.W., Billica, R.D., et al.: Endoscopic surgery in weightlessness: the investigation of basic principles for surgery in space. Surg. Endoscopic. 15, 1413–1418 (2001)

    Google Scholar 

  • Campbell, M.R., Williams, D.R., Buckey, J.C. Jr, Kirkpatrick, A.W.: Animal surgery during spaceflight on the Neurolab Shuttle mission. Aviat. Space. Environ. Med. 76(6), 589–593 (2005)

    Google Scholar 

  • Chung, C.Y., Erickson, H.P.: Glycosaminoglycans modulate fibronectin matrix assembly and are essential for matrix incorporation of tenascin-C. J. Cell. Sci. 110(Pt 12), 1413–1419 (1997)

    Google Scholar 

  • Cogoli, A.: Signal transduction in T lymphocytes in microgravity. Gravit. Space. Biol. Bull. 10(2), 5–16 (1997)

    Google Scholar 

  • Colognato, H., Yurchenco, P.D.: Form and function: the laminin family of heterotrimers. Dev. Dyn. 218(2), 213–234 (2000)

    Article  Google Scholar 

  • Davidson, J., Aquino, A., Woodward, S., et al.: Sustained microgravity reduces intrinsic wound healing and growth factor responses in the rat. FASEB J. 13(2), 325–329 (1999)

    Google Scholar 

  • Delp, M.D.: Unraveling the complex web of impaired wound healing with mechanical unloading and physical deconditioning. J. Appl. Physiol. 104, 1262–1263 (2008)

    Article  Google Scholar 

  • Grimm, D., Infanger, M., Westphal, K., Ulbrich, C., Pietsch, J., Kossmehl, P., Vadrucci, S., Baatout, S., Flick, B., Paul, M., Bauer, J.: A delayed type of three-dimensional growth of human endothelial cells under simulated weightlessness. Tissue Eng. Part. A. 15(8), 2267–2275 (2009)

    Article  Google Scholar 

  • Guarnieri, D., Battista, S., Borzacchiello, A., Mayol, L., De Rosa, E., Keene, D.R., Muscariello, L., Barbarisi, A., Netti, P.A.: Effects of fibronectin and laminin on structural, mechanical and transport properties of 3D collageneous network. J. Mater. Sci. Mater. Med. 18(2), 245–253 (2007)

    Article  Google Scholar 

  • Heinemeier, K.M., Olesen, J.L., Haddad, F., Schjerling, P., Baldwin, K.M., Kjaer, M.: Effect of unloading followed by reloading on expression of collagen and related growth factors in rat tendon and muscle. J. Appl. Physiol. 106(1), 178–186 (2009) Epub 2008 Nov 6

    Article  Google Scholar 

  • Hughes-Fulford, M., Gilbertson, V.: Osteoblast fibronectin mRNA, protein synthesis, and matrix are unchanged after exposure to microgravity. FASEB J. 13, S121–S127 (1999)

    Google Scholar 

  • Juergensmeyer, M.A., Juergensmeyer, E.A., Guikema, J.A.: Long-term exposure to spaceflight conditions affects bacterial response to antibiotics. Microgravity Sci. Technol. 12(1), 41–47 (1999)

    Google Scholar 

  • Karu, T.: Photobiology of low-power laser effects. Health Phys. 56(5), 691–704 (1989)

    Article  Google Scholar 

  • Lamponi, S., Di Canio, C., Barbucci, R.: Heterotypic cell–cell interaction on micropatterned surfaces. Int. J. Artif. Organs. 32(8), 507–516 (2009)

    Google Scholar 

  • Li, J., Zhang, Y.P., Kirsner, R.S.: Angiogenesis in wound repair: angiogenic growth factors and the extracellularmatrix. Microsc. Res. Tech. 60(1), 107–114 (2003)

    Article  Google Scholar 

  • Loesberg, W.A., Walboomers, X.F., Bronkhorst, E.M., van Loon, J.J., Jansen, J.A.: The effect of combined simulated microgravity and microgrooved surface topography on fibroblasts. Cell Motil. Cytoskeleton. 64(3), 174–185 (2007)

    Article  Google Scholar 

  • Martinez, D.A., Vailas, A.C., Vanderby, R. Jr, Grindeland, R.E.: Temporal extracellular matrix adaptations in ligament during wound healing and hindlimb unloading. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293, 1552–1560 (2007)

    Article  Google Scholar 

  • McCuaig, K., Lloyd, C.W., Gosbee, J., Snyder, W.W.: Simulation of blood flow in microgravity. Am. J. Surg. 164, 119–123 (1992)

    Article  Google Scholar 

  • Midura, R.J., Su, X., Androjna, C.: A simulated weightlessness state diminishes cortical bone healing responses. J. Musculoskelet. Neuronal. Interact. 6(4), 327–328 (2006)

    Google Scholar 

  • Monici, M., Basile, V., Cialdai, F., Romano, G., Fusi, F., Conti, A.: Irradiation by pulsed Nd:YAG laser induces the production of extracellular matrix molecules by cells of the connective tissues. A tool for tissue repair. In: Popp, J., Drexler, W., Turchin, V.V., Matthews, D.L. (eds.) Biophotonics: photonic solutions for Better Health Care, Proc. of SPIE, vol. 6991, 69912K1-10. doi:10.1117/12.782865 (2008a)

  • Monici, M., Romano, G., Cialdai, F., Fusi, F., Marziliano, N., Benvenuti, S., Cellai, I., Egli, M., Cogoli, A.: Gravitational/mechanical factors affect gene expression profile and phenotypic specification of human mesenchymal stem cells. J. Gravit. Physiol. 15(1), 191–192 (2008b)

    Google Scholar 

  • Morbidelli, L., Monici, M., Marziliano, N., Cogoli, A., Fusi, F., Waltenberger, J., Ziche, M.: Simulated hypogravity impairs the angiogenic response of endothelium by up-regulating apoptotic signals. Biochem. Biophys. Res. Com. 334, 491–499 (2005)

    Article  Google Scholar 

  • Ninomiya, T., Miyamoto, Y., Ito, T., Yamashita, A., Wakita, M., Nishisaka, T.: High-intensity pulsed laser irradiation accelerates bone formation in metaphyseal trabecular bone in rat femur. J. Bone Miner. Metab. 21(2), 67–73 (2003)

    Article  Google Scholar 

  • Pankov, R., Yamada, K.M.: Fibronectin at a glance. J. Cell Science 115, 3861–3863 (2002)

    Article  Google Scholar 

  • Peplow, P.V., Chung, T.Y., Baxter, G.D.: Laser photobiomodulation of wound healing: a review of experimental studies in mouse and rat animal models. Photomed. Laser Surg. 28(3), 291–325 (2010)

    Article  Google Scholar 

  • Provenzano, P.P., Martinez, D.A., Grindeland, R.E., Dwyer, K.W., Turner, J., Vailas, A.C., Vanderby, R. Jr: Hindlimb unloading alters ligament healing. J. Appl. Physiol. 94(1), 314–324 (2003) Epub 2002

    Google Scholar 

  • Radek, K.A., Baer Lisa, A., Eckhardt, J., DiPietro, L.A., Wade, C.E.: Mechanical unloading impairs keratinocyte migration and angiogenesis during cutaneous wound healing. J. Appl. Physiol. 104, 1295–1303 (2008)

    Article  Google Scholar 

  • Robertson, D., Convertino, V.A., Vernikos, J.: The sympathetic nervous system and the physiologic consequences of spaceflight: a hypothesis. Am. J. Med. Sci. 308, 126–132 (1994)

    Article  Google Scholar 

  • Rossi, F., Pini, R., Monici, M.: Direct and indirect photomechanical effects in cells and tissues. Perspectives of application in biotechnology and medicine. In: Monici, M., van Loon, J. (eds.) Cell Mechanochemistry. Biological systems and factors inducing mechanical stress, such as light, pressure and gravity. Research Signpost/Transword Research Network, pp. 285–301, Trivandrum, India (2010)

  • Schelling, M.E., Meininger, C.J., Hawker, J.R. Jr., Granger, H.J.: Venular endothelial cells from bovine heart. Am. J. Physiol. 254, H1211–H1217 (1988)

    Google Scholar 

  • Seitzer, U., Bodo, M., Müller, P.K., Açil, Y., Bätge, B.: Microgravity and hypergravity effects on collagen biosynthesis of human dermal fibroblasts. Cell. Tissue Res. 282(3), 513–517 (1995)

    Article  Google Scholar 

  • Stern, R., Asari, A.A., Sugahara, K.N.: Hyaluronan fragments: an information-rich system. Eur. J. Cell Biol. 85(8), 699–715 (2006)

    Article  Google Scholar 

  • Tettamanti, G., Grimaldi, A., Rinaldi, L., Arnaboldi, F., Congiu, T., Valvassori, R., de Eguileor, M.: The multifunctional role of fibroblasts during wound healing in Hirudo medicinalis (Annelida, Hirudinea). Biol. Cell 96, 443–455 (2004)

    Article  Google Scholar 

  • Valent, A., Pratesi, R., Monici, M., Fusi, F.: Hilterapia® Manual. ASAcampus, ASA Research Division (eds.) Arcugnano (VI) Italy (2009)

  • Virchenko, O., Aspenberg, P.: How can one platelet injection after tendon injury lead to a stronger tendon after 4 weeks? Interplay between early regeneration and mechanical stimulation. Acta Orthopaedica. 77(5), 806–812 (2006)

    Article  Google Scholar 

  • Vogel, A., Venugopalan, V.: Mechanisms of pulsed laser ablation of biological tissues. Chem. Rev. 103, 577–644 (2003)

    Article  Google Scholar 

  • Whelan, H., Desmet, K., Buchmann, E., Henry, M., Wong-Riley, M., Eells, J., Verhoeve, J.: Harnessing the cell’s own ability to repair and prevent neurodegenerative disease. SPIE Newsroom. 24, 1–3 (2008)

    Google Scholar 

  • Widgerow, A.D., Chait, L.A., Stals, R., Stals, P.J.: New innovations in scar management. Aesthetic. Plast. Surg. 24(3), 227–234 (2000)

    Article  Google Scholar 

  • Wong, B.J., Pandhoh, N., Truong, M.T., Diaz, S., Chao, K., Hou, S., Gardiner, D.: Identification of chondrocyte proliferation following laser irradiation, thermal injury, and mechanical trauma. Lasers Surg. Med. 37(1), 89–96 (2005)

    Article  Google Scholar 

  • Wu, C., Keivens, V.M., O’Toole, T.E., McDonald, J.A., Ginsberg, M.H.: Integrin activation and cytoskeletal interaction are essential for the assembly of a fibronectin matrix. Cell 83, 715–724 (1995)

    Article  Google Scholar 

  • Zati, A., Fortuna, D., Valent, A., Filippi, M.V., Bilotta, T.W.: High intensity laser therapy (HILT) versus TENS and NSAIDs in low back pain: clinical study. Proc. SPIE. 5610, 277–283 (2004)

    Article  Google Scholar 

  • Zhang, Q., Magnusson, M.K., Mosher, D.F.: Lysophosphatidic acid and microtubule-destabilizing agents stimulate fibronectin matrix assembly through Rho-dependent actin stress fiber formation and cell contraction. Mol. Biol. Cell. 8, 1415–1425 (1997)

    Google Scholar 

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Authors and Affiliations

  1. ASAcampus Joint Laboratory, ASA Research Division, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy

    Monica Monici

  2. Department of Clinical Physiopathology, University of Florence, Florence, Italy

    Francesca Cialdai, Giovanni Romano & Franco Fusi

  3. Space Biology Group, ETH-Technopark, Zurich, Switzerland

    Marcel Egli

  4. Section of Pharmacology, Department of Molecular Biology, University of Siena, Siena, Italy

    Silvia Pezzatini & Lucia Morbidelli

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  1. Monica Monici
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  2. Francesca Cialdai
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  3. Giovanni Romano
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  4. Franco Fusi
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  5. Marcel Egli
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  6. Silvia Pezzatini
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  7. Lucia Morbidelli
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Correspondence to Monica Monici.

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Monici, M., Cialdai, F., Romano, G. et al. An in Vitro Study on Tissue Repair: Impact of Unloading on Cells Involved in the Remodelling Phase. Microgravity Sci. Technol. 23, 391–401 (2011). https://doi.org/10.1007/s12217-011-9259-4

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