Duration of simulated microgravity affects the differentiation of mesenchymal stem cells

Xue,Li; Li,Yaohui; Chen,Jun

doi:10.3892/mmr.2017.6357

Duration of simulated microgravity affects the differentiation of mesenchymal stem cells

Authors:
- Li Xue
- Yaohui Li
- Jun Chen
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Affiliations: Department of Urology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710014, P.R. China, Department of Pneumology, Traditional Chinese Medicine Hospital of Shaanxi, Xi'an, Shaanxi 710014, P.R. China, Department of Encephalopathy, Traditional Chinese Medicine Hospital of Shaanxi, Xi'an, Shaanxi 710014, P.R. China
Published online on: March 22, 2017 https://doi.org/10.3892/mmr.2017.6357
Pages: 3011-3018
Copyright: © Xue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous evidence has suggested that physical microenvironments and mechanical stresses, independent of soluble factors, influence mesenchymal stem cell (MSC) fate. In the present study, simulated microgravity (SMG) was demonstrated to regulate the differentiation of mesenchymal stem cells. This may be a novel strategy for tissue engineering and regenerative medicine. Rat MSCs were cultured for 72 h or 10 days in either normal gravity or a clinostat to model microgravity, followed with culture in diverse differential media. A short period of stimulation (72 h) promoted MSCs to undergo endothelial, neuronal and adipogenic differentiation. In comparison, extended microgravity (10 days) promoted MSCs to differentiate into osteoblasts. A short period of exposure to SMG significantly decreased ras homolog family member A (RhoA) activity. However, RhoA activity significantly increased following prolonged exposure to SMG. When RhoA activity was inhibited, the effects of prolonged exposure to SMG were reversed. These results demonstrated that the duration of SMG regulates the differentiation fate of MSCs via the RhoA‑associated pathway.

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1	Langer R and Vacanti JP: Tissue engineering. Science. 260:920–926. 1993. View Article : Google Scholar : PubMed/NCBI
2	Grimm D, Bauer J, Kossmehl P, Shakibaei M, Schöberger J, Pickenhahn H, Schulze-Tanzil G, Vetter R, Eilles C, Paul M and Cogoli A: Simulated microgravity alters differentiation and increases apoptosis in human follicular thyroid carcinoma cells. FASEB J. 16:604–606. 2002.PubMed/NCBI
3	Hochleitner B, Hengster P, Duo L, Bucher H, Klima G and Margreiter R: A novel bioartificial liver with culture of porcine hepatocyte aggregates under simulated microgravity. Artif Organs. 29:58–66. 2005. View Article : Google Scholar : PubMed/NCBI
4	Marquette ML, Byerly D and Sognier M: A novel in vitro three-dimensional skeletal muscle model. In Vitro Cell Dev Biol Anim. 43:255–263. 2007. View Article : Google Scholar : PubMed/NCBI
5	Yuge L, Kajiume T, Tahara H, Kawahara Y, Umeda C, Yoshimoto R, Wu SL, Yamaoka K, Asashima M, Kataoka K and Ide T: Microgravity potentiates stem cell proliferation while sustaining the capability of differentiation. Stem Cells Dev. 15:921–929. 2006. View Article : Google Scholar : PubMed/NCBI
6	Huang Y, Dai ZQ, Ling SK, Zhang HY, Wan YM and Li YH: Gravity, a regulation factor in the differentiation of rat bone marrow mesenchymal stem cells. J Biomed Sci. 16:872009. View Article : Google Scholar : PubMed/NCBI
7	Chen J, Liu R, Yang Y, Li J, Zhang X, Wang Z and Ma J: The simulated microgravity enhances the differentiation of mesenchymal stem cells into neurons. Neurosci Lett. 505:171–175. 2011. View Article : Google Scholar : PubMed/NCBI
8	Dai ZQ, Wang R, Ling SK, Wan YM and Li YH: Simulated microgravity inhibits the proliferation and osteogenesis of rat bone marrow mesenchymal stem cells. Cell Prolif. 40:671–684. 2007. View Article : Google Scholar : PubMed/NCBI
9	McBeath R, Pirone DM, Nelson CM, Bhadriraju K and Chen CS: Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell. 6:483–495. 2004. View Article : Google Scholar : PubMed/NCBI
10	Kilian KA, Bugarija B, Lahn BT and Mrksich M: Geometric cues for directing the differentiation of mesenchymal stem cells. Proc Natl Acad Sci USA. 107:4872–4877. 2010. View Article : Google Scholar : PubMed/NCBI
11	Hughes-Fulford M and Lewis ML: Effects of microgravity on osteoblast growth activation. Exp Cell Res. 224:103–109. 1996. View Article : Google Scholar : PubMed/NCBI
12	Schatten H, Lewis ML and Chakrabarti A: Spaceflight and clinorotation cause cytoskeleton and mitochondria changes and increases in apoptosis in cultured cells. Acta Astronaut. 49:399–418. 2001. View Article : Google Scholar : PubMed/NCBI
13	Uva BM, Masini MA, Sturla M, Prato P, Passalacqua M, Giuliani M, Tagliafierro G and Strollo F: Clinorotation-induced weightlessness influences the cytoskeleton of glial cells in culture. Brain Res. 934:132–139. 2002. View Article : Google Scholar : PubMed/NCBI
14	Hall A: Rho GTPases and the actin cytoskeleton. Science. 279:509–514. 1998. View Article : Google Scholar : PubMed/NCBI
15	Azizi SA, Stokes D, Augelli BJ, DiGirolamo C and Prockop DJ: Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats-similarities to astrocyte grafts. Proc Natl Acad Sci USA. 95:3908–3913. 1998. View Article : Google Scholar : PubMed/NCBI
16	Wang X, Ren Q, Fu S and Jiang P: Development and application of clinostat for simulation of microgravity biological effects. Acta Biophysica Sinica. 13:161–166. 1997.
17	Jiang J, Lv Z, Gu Y, Li J, Xu L, Xu W, Lu J and Xu J: Adult rat mesenchymal stem cells differentiate into neuronal-like phenotype and express a variety of neuro-regulatory molecules in vitro. Neurosci Res. 66:46–52. 2010. View Article : Google Scholar : PubMed/NCBI
18	Jaiswal N, Haynesworth SE, Caplan AI and Bruder SP: Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem. 64:295–312. 1997. View Article : Google Scholar : PubMed/NCBI
19	Oswald J, Boxberger S, Jorgensen B, Feldmann S, Ehninger G, Bornhäuser M and Werner C: Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells. 22:377–384. 2004. View Article : Google Scholar : PubMed/NCBI
20	Xiang Y, Zheng Q, Jia B, Huang G, Xie C, Pan J and Wang J: Ex vivo expansion, adipogenesis and neurogenesis of cryopreserved human bone marrow mesenchymal stem cells. Cell Biol Int. 31:444–450. 2007. View Article : Google Scholar : PubMed/NCBI
21	Spiegelman BM and Ginty CA: Fibronectin modulation of cell shape and lipogenic gene expression in 3T3-adipocytes. Cell. 35:657–666. 1983. View Article : Google Scholar : PubMed/NCBI
22	Baksh D, Song L and Tuan RS: Adult mesenchymal stem cells: Characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med. 8:301–316. 2004. View Article : Google Scholar : PubMed/NCBI
23	Zayzafoon M, Gathings WE and McDonald JM: Modeled microgravity inhibits osteogenic differentiation of human mesenchymal stem cells and increases adipogenesis. Endocrinology. 145:2421–2432. 2004. View Article : Google Scholar : PubMed/NCBI
24	Buravkova L, Romanov Y, Rykova M, Grigorieva O and Merzlikina N: Cell-to-cell interactions in changed gravity: Ground-based and flight experiments. Acta Astronaut. 57:67–74. 2005. View Article : Google Scholar : PubMed/NCBI
25	McBeath R, Pirone DM, Nelson CM, Bhadriraju K and Chen CS: Cell shape, cytoskeletal tension, and rhoa regulate stem cell lineage commitment. Dev Cell. 6:483–495. 2004. View Article : Google Scholar : PubMed/NCBI
26	Carnac G, Primig M, Kitzmann M, Chafey P, Tuil D, Lamb N and Fernandez A: RhoA GTPase and serum response factor control selectively the expression of MyoD without affecting Myf5 in mouse myoblasts. Mol Biol Cell. 9:1891–1902. 1998. View Article : Google Scholar : PubMed/NCBI
27	Sordella R, Jiang W, Chen GC, Curto M and Settleman J: Modulation of Rho GTPase signaling regulates a switch between adipogenesis and myogenesis. Cell. 113:147–158. 2003. View Article : Google Scholar : PubMed/NCBI
28	Young KG and Copeland JW: Formins in cell signaling. Biochim Biophys Acta. 1803:183–190. 2010. View Article : Google Scholar : PubMed/NCBI
29	Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K and Narumiya S: Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science. 285:895–898. 1999. View Article : Google Scholar : PubMed/NCBI
30	Hotulainen P and Lappalainen P: Stress fibers are generated by two distinct actin assembly mechanisms in motile cells. J Cell Biol. 173:383–394. 2006. View Article : Google Scholar : PubMed/NCBI