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Simulated microgravity inhibits the migration of mesenchymal stem cells by remodeling actin cytoskeleton and increasing cell stiffness

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Abstract

Exposure to microgravity during space flight affects almost all human physiological systems. Migration, proliferation, and differentiation of stem cells are crucial for tissues repair and regeneration. However, the effect of microgravity on the migration potentials of bone marrow mesenchymal stem cells (BMSCs) is unclear, which are important progenitor and supporting cells. Here, we utilized a clinostat to model simulated microgravity (SMG) and found that SMG obviously inhibited migration of rat BMSCs. We detected significant reorganization of F-actin filaments and increased Young’s modulus of BMSCs after exposure to SMG. Moreover, Y-27632 (a specific inhibitor of ROCK) abrogated the inhibited migration capacity and polymerized F-actin filament of BMSCs under SMG. Interestingly, we found that transferring BMSCs to normal gravity also attenuated the polymerized F-actin filament and Young’s modulus of BMSCs induced by SMG, but could not recover migration capacity of BMSCs inhibited by SMG. Taken together, we propose that SMG inhibits migration of BMSCs through remodeling F-actin and increasing cell stiffness.

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References

  • Callan-Jones AC, Voituriez R (2016) Actin flows in cell migration: from locomotion and polarity to trajectories. Curr Opin Cell Biol 38:12–17

    Article  CAS  Google Scholar 

  • Dai ZQ, Wang R, Ling SK, Wan YM, Li YH (2007) Simulated microgravity inhibits the proliferation and osteogenesis of rat bone marrow mesenchymal stem cells. Cell Prolif 40:671–684

    Article  CAS  Google Scholar 

  • Friedl P, Wolf K, Lammerding J (2011) Nuclear mechanics during cell migration. Curr Opin Cell Biol 23:55–64

    Article  CAS  Google Scholar 

  • Hopkins AM, Pineda AA, Winfree LM, Brown GT, Laukoetter MG, Nusrat A (2006) Organized migration of epithelial cells requires control of adhesion and protrusion through Rho kinase effectors. Am J Physiol Gastrointest Liver Physiol 292:806–817

    Article  Google Scholar 

  • Jhala DV, Kale RK, Singh RP (2014) Microgravity alters cancer growth and progression. Curr Cancer Drug Targets 14:394–406

    Article  CAS  Google Scholar 

  • Lange JR, Fabry B (2013) Fabry: cell and tissue mechanics in cell migration. Exp Cell Res 319:2418–2423

    Article  CAS  Google Scholar 

  • Lee SH, Dominguez R (2010) Regulation of actin cytoskeleton dynamics in cells. Mol Cells 29:311–325

    Article  CAS  Google Scholar 

  • Li J, Zhang S, Chen J, Du T, Wang Y, Wang Z (2009) Modeled microgravity causes changes in the cytoskeleton and focal adhesions, and decreases in migration in malignant human MCF-7 cells. Protoplasma 238:23–33

    Article  Google Scholar 

  • Li J, Guo W, Xiong M, Han H, Chen J, Mao D, Tang B, Yu H, Zeng Y (2015) Effect of SDF-1/CXCR4 axis on the migration of transplanted bone mesenchymal stem cells mobilized by erythropoietin toward lesion sites following spinal cord injury. Int J Mol Med 36:1205–1214

    CAS  Google Scholar 

  • Louis F, Deroanne C, Nusgens B, Vico L, Guignandon A (2015) RhoGTPases as key players in mammalian cell adaptation to microgravity. Biomed Res Int 2015:747693

    Google Scholar 

  • Maier JA, Cialdai F, Monici M, Morbidelli L (2015) The impact of microgravity and hypergravity on endothelial cells. Biomed Res Int 2015:434803

    Article  Google Scholar 

  • Meloni MA, Galleri G, Pani G, Saba A, Pippia P, Cogoli-Greuter M (2011) Space flight affects motility and cytoskeletal structures in human monocyte cell line J-111. Cytoskeleton 68:125–137

    Article  CAS  Google Scholar 

  • Meyers VE, Zayzafoon M, Douglas JT, McDonald JM (2005) RhoA and cytoskeletal disruption mediate reduced osteoblastogenesis and enhanced adipogenesis of human mesenchymal stem cells in modeled microgravity. J Bone Miner Res 20:1858–1866

    Article  CAS  Google Scholar 

  • Mitsuhara T, Takeda M, Yamaguchi S, Manabe T, Matsumoto M, Kawahara Y, Yuge L, Kurisu K (2013) Simulated microgravity facilitates cell migration and neuroprotection after bone marrow stromal cell transplantation in spinal cord injury. Stem Cell Res Ther 4:35–45

    Article  CAS  Google Scholar 

  • Nakashima M, Lazo JS (2010) Phosphatase of regenerating liver-1 promotes cell migration and invasion and regulates filamentous actin dynamics. J Pharmacol Exp Ther 334:627–633

    Article  CAS  Google Scholar 

  • Paulsen K, Tauber S, Dumrese C, Bradacs G, Simmet DM, Golz N, Hauschild S, Raig C, Engeli S, Gutewort A, Hurlimann E, Biskup J, Unverdorben F, Rieder G, Hofmanner D, Mutschler L, Krammer S, Buttron I, Philpot C, Huge A, Lier H, Barz I, Engelmann F, Layer LE, Thiel CS, Ullrich O (2015) Regulation of ICAM-1 in cells of the monocyte/macrophage system in microgravity. Biomed Res Int 2015:538786

    Article  Google Scholar 

  • Plett PA, Abonour R, Frankovitz S, Orschell CM (2004) Impact of modeled microgravity on migration, differentiation, and cell cycle control of primitive human hematopoietic progenitor cells. Exp Hematol 32:773–781

    Article  CAS  Google Scholar 

  • See EY, Toh SL, Goh JC (2010) Multilineage potential of bone-marrow-derived mesenchymal stem cell cell sheets: implications for tissue engineering. Tissue Eng Part A 16:1421–1431

    Article  CAS  Google Scholar 

  • Siamwala JH, Reddy SH, Majumder S, Kolluru GK, Muley A, Sinha S, Chatterjee S (2010) Simulated microgravity perturbs actin polymerization to promote nitric oxide-associated migration in human immortalized Eahy926 cells. Protoplasma 242:3–12

    Article  CAS  Google Scholar 

  • Wang R, Bi J, Ampah KK, Ba X, Liu W, Zeng X (2013) Lipid rafts control human melanoma cell migration by regulating focal adhesion disassembly. Biochim Biophys Acta 1833:3195–3205

    Article  CAS  Google Scholar 

  • Wang N, Wang H, Chen J, Zhang X, Xie J, Li Z, Ma J, Wang W, Wang Z (2014) The simulated microgravity enhances multipotential differentiation capacity of bone marrow mesenchymal stem cells. Cytotechnology 66:119–131

    Article  CAS  Google Scholar 

  • Wehland M, Ma X, Braun M, Hauslage J, Hemmersbach R, Bauer J, Grosse J, Infanger M, Grimm D (2013) The impact of altered gravity and vibration on endothelial cells during a parabolic flight. Cell Physiol Biochem 31:432–451

    Article  CAS  Google Scholar 

  • Yan M, Wang Y, Yang M, Liu Y, Qu B, Ye Z, Liang W, Sun X, Luo Z (2015) The effects and mechanisms of clinorotation on proliferation and differentiation in bone marrow mesenchymal stem cells. Biochem Biophys Res Commun 460:327–332

    Article  CAS  Google Scholar 

  • Zayzafoon M, Meyers VE, McDonald JM (2005) Microgravity: the immune response and bone. Immunol Rev 208:267–280

    Article  CAS  Google Scholar 

  • Zhang C, Li L, Chen J, Wang J (2015a) Behavior of stem cells under outer-space microgravity and ground-based microgravity simulation. Cell Biol Int 39:647–656

    Article  Google Scholar 

  • Zhang B, Luo Q, Chen Z, Sun J, Xu B, Ju Y, Song G (2015b) Cyclic mechanical stretching promotes migration but inhibits invasion of rat bone marrow stromal cells. Stem Cell Res 14:155–164

    Article  CAS  Google Scholar 

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Acknowledgments

We thank Prof. Long and Dr. Sun for crucial advice of the clinostat. This work was supported by Grants from the National Basic Research Program of China (2011CB710900), the Key Laboratory of Microgravity, Institute of Mechanics, Chinese Academy of Sciences (NML1516KFKT4-4), the National Natural Science Foundation of China (11272365, 11511140092, 11532004), the Fundamental Research Funds for the Central Universities (106112015CDJZR238807), the Research Fund for the Doctoral Program of Higher Education of China (20130191110029), and the Visiting Scholar Foundation of Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education (CQKLBST-2015-008).

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  1. Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China

    Xinjian Mao, Zhe Chen, Qing Luo, Bingyu Zhang & Guanbin Song

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  1. Xinjian Mao
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  2. Zhe Chen
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  3. Qing Luo
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  4. Bingyu Zhang
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  5. Guanbin Song
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Correspondence to Guanbin Song.

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Mao, X., Chen, Z., Luo, Q. et al. Simulated microgravity inhibits the migration of mesenchymal stem cells by remodeling actin cytoskeleton and increasing cell stiffness. Cytotechnology 68, 2235–2243 (2016). https://doi.org/10.1007/s10616-016-0007-x

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  • DOI: https://doi.org/10.1007/s10616-016-0007-x

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