Skip to main content
Log in

Model microgravity enhances endothelium differentiation of mesenchymal stem cells

  • Original Paper
  • Published:
Naturwissenschaften Aims and scope Submit manuscript

Abstract

Mesenchymal stem cells (MSCs) are capable of differentiation into multilineage cell types under certain induction conditions. Previous studies have demonstrated that physical environments and mechanical force can influence MSC fate, indicating that these factors may be favorable inducers for clinical treatment. Our previous study found that MSCs are spread with a spindle shape when cultured in normal gravity (NG), and under modeled microgravity (MMG) for 72 h, they become unspread and round and their cytoskeleton fibers are reorganized. These morphological changes affected the function of MSCs through the activity of RhoA. We examined the responses of MSCs under MMG stimulation, followed with VEGF differentiation. We found that MSCs under MMG for 72 h were differentiated into endothelial-like cells by detecting the expression of endothelial-specific molecules (Flk-1 and vWF), which were also able to form a capillary network. Their endothelial differentiation potential was improved under MMG compared with that under NG. We believe that this method is a novel choice of MMG stimulation for neovascularization. This phenomenon may increase the potential of MSC differentiation, which might be a new strategy for the treatment of various vascular diseases and improve vascularization in tissue engineering.

This is a preview of subscription content, log in via an institution to check access.

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Aguirre A, Planell JA, Engel E (2010) Dynamics of bone marrow-derived endothelial progenitor cell/mesenchymal stem cell interaction in co-culture and its implications in angiogenesis. Biochem Biophys Res Commun 400(2):284–291

    Article  PubMed  CAS  Google Scholar 

  • Amos LA, Ent F, Lowe J (2004) Structural/functional homology between the bacterial and eukaryotic cytoskeletons. Curr Opin Cell Biol 16:24–31

    Article  PubMed  CAS  Google Scholar 

  • Banuett F, Herskowitz I (2002) Bud morphogenesis and the actin and microtubule cytoskeletons during budding in the corn smut fungus, Ustilago maydis. Fungal Genet Biol 37:149–170

    Article  PubMed  Google Scholar 

  • Bauer E, Sumpio J, Timothy R, Alan D (2002) Cells in focus: endothelial cell. Int J Biochem Cell B 34:1508–1512

    Article  Google Scholar 

  • Bernardo ME, Locatelli F, Fibbe WE (2009) Mesenchymal stromal cells: a novel treatment modality for tissue repair. Ann N Y Acad Sci 1176:101–117

    Article  PubMed  CAS  Google Scholar 

  • Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380:435–439

    Article  PubMed  CAS  Google Scholar 

  • Cau J, Hall A (2005) Cdc42 controls the polarity of the actin and microtubule cytoskeletons through two distinct signal transduction pathways. J Cell Sci 118:2579–2587

    Article  PubMed  CAS  Google Scholar 

  • Chen MY, Lie PC, Li ZL, Wei X (2009) Endothelial differentiation of Wharton's jelly-derived mesenchymal stem cells in comparison with bone marrow-derived mesenchymal stem cells. Exp Hematol 37:629–640

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Liu R, YangY LJ, Zhang X, Li J, Wang Z, Ma J (2011) The simulated microgravity enhances the differentiation of mesenchymal stem cells into neurons. Neurosci Lett 505:171–175

    Article  PubMed  CAS  Google Scholar 

  • Chesarone MA, DuPage AG, Goode BL (2010) Unleashing formins to remodel the actin and microtubule cytoskeletons. Nat Rev Mol Cell Biol 11(1):62–74

    Article  PubMed  CAS  Google Scholar 

  • Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25(4):581–611

    Article  PubMed  CAS  Google Scholar 

  • Guignandon A, Lafage-Proust MH, Usson Y, Laroche N, Caillot-Augusseau A, Alexandre C, Vico L (2001) Cell cycling determines integrin-mediated adhesion in osteoblastic ROS 17/2.8 cells exposed to space-related conditions. FASEB J 15:2036–2038

    PubMed  CAS  Google Scholar 

  • Hall A (1998) Rho GTPases and the actin cytoskeleton. Science 279(5350):509–514

    Article  PubMed  CAS  Google Scholar 

  • Hosu BG, Mullen SF, Critser JK, Forgacs G (2008) Reversible disassembly of the actin cytoskeleton improves the survival rate and developmental competence of cryopreserved mouse oocytes. PLoS One 3(7):p.e2787

    Article  Google Scholar 

  • Hotulainen P, Lappalainen P (2006) Stress fibers are generated by two distinct actin assembly mechanisms in motile cells. J Cell Biol 173:383–394

    Article  PubMed  CAS  Google Scholar 

  • Hu Y, Davison F, Zhang Z, Xu Q (2003) Endothelial replacement and angiogenesis in arteriosclerotic lesions of allografts are contributed by circulating progenitor cells. Circulation 108:3122–3127

    Article  PubMed  Google Scholar 

  • Huang Y, Dai ZQ, Ling SK, Zhang HY, Wan YM, Li YH (2009) Gravity, a regulation factor in the differentiation of rat bone marrow mesenchymal stem cells. J Biomed Sci 16:87–98

    Article  PubMed  Google Scholar 

  • Ingher D (1999) How cells (might) sense microgravity. FASEB J 13(suppl):s3–s15

    Google Scholar 

  • Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49

    Article  PubMed  CAS  Google Scholar 

  • Kasper G, Dankert N, Tuischer J, Hoeft M, Gaber T, Glaeser JD, Zander D, Tschirschmann M, Thompson M, Matziolis G, Duda GN (2007) Mesenchymal stem cells regulate angiogenesis according to their mechanical environment. Stem Cells 25:903–910

    Article  PubMed  CAS  Google Scholar 

  • Koh-Ichi N, Inagaki M (2005) Cytoskeletal modification of Rho guanine nucleotide exchange factor activity: identification of a Rho guanine nucleotide exchange factor as a binding partner for Sept9b, a mammalian septin. Oncogene 24:65–76

    Article  Google Scholar 

  • Langer R, Vacanti JP (1993) Tissue engineering. Science 260(5110):920–926

    Article  PubMed  CAS  Google Scholar 

  • Levenberg S (2005) Engineering blood vessels from stem cells: recent advances and applications. Curr Opin Biotechnol 16:516–523

    Article  PubMed  CAS  Google Scholar 

  • Levenberg S, Rouwkema J, Macdonald M, Garfein ES, Kohane DS, Darland DC, Marini R, Blitterswijk CA, Mulligan RC, D'Amore PA, Langer R (2005) Engineering vascularized skeletal muscle tissue. Nat Biotechnol 23(7):879–884

    Article  PubMed  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  PubMed  Google Scholar 

  • McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS (2004) Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell 6:483–495

    Article  PubMed  CAS  Google Scholar 

  • McIntosh K, Zvonic S, Garrett S, Mitchell JB, Floyd ZE, Hammill L, Kloster A, Halvorsen YD, Ting JP, Storms RW, Goh B, Kilroy G, Wu X, Gimble JM (2006) The immunogenicity of human adipose-derived cells: temporal changes in vitro. Stem Cells 24:1246–1253

    Article  PubMed  CAS  Google Scholar 

  • Meyers VE, Zayzafoon M, Gonda SR, Gathings WE, McDonald JM (2004) Modeled microgravity disrupts collagen I/integrin signaling during osteoblastic differentiation of human mesenchymal stem cells. J Cell Biochem 93:697–704

    Article  PubMed  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 20:1858–1867

    Article  PubMed  CAS  Google Scholar 

  • Mitchell JB, McIntosh K, Zvonic S, Garrett S, Floyd ZE, Kloster A, Halvorsen YD, Storms RW, Goh B, Kilroy G, Wu X, Gimble JM (2006) Immunophenotype of human adipose derived cells: temporal changes in stromal-associated and stem cell-associated markers. Stem Cells 24:376–385

    Article  PubMed  Google Scholar 

  • Nomi M, Atala A, Coppi PD, Soker S (2002) Principals of neovascularization for tissue engineering. Mol Aspect Med 23(6):463–483

    Article  CAS  Google Scholar 

  • Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anvers P (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705

    Article  PubMed  CAS  Google Scholar 

  • Oswald J, Boxberger S, Jorgensen B, Feldmann S, Ehninger G, Bornhauser M, Werner C (2004) Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells 22(3):377–384

    Article  PubMed  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147

    Article  PubMed  CAS  Google Scholar 

  • Ruggeri ZM (2003) Von Willebrand factor, platelets and endothelial cell interactions. J Thromb Haemost 1(7):1335–1342

    Article  PubMed  CAS  Google Scholar 

  • Sadowitz B, Seymour K, Costanza MJ, Gahtan V (2010) Statin therapy—part II: clinical considerations for cardiovascular disease. Vasc Endovasc Surg 44:421–433

    Article  Google Scholar 

  • Sambandam Y, Blanchard JJ, Daughtridge G, Kolb RJ, Shanmugarajan S, Pandruvada SN, Bateman TA, Reddy SV (2010) Microarray profile of gene expression during osteoclast differentiation in modelled microgravity. J Cell Biochem 111:1179–1187

    Article  PubMed  CAS  Google Scholar 

  • Stolzing A, Jones E, McGonagle D, Scutt A (2008) Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev 129:163–173

    Article  PubMed  CAS  Google Scholar 

  • Talens-Visconti R, Bonora A, Jover R, Mirabet V, Carbonell F, Castell JV, Gomez-Lechon MJ (2006) Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells. World J Gastroenterol 12:5834–5845

    PubMed  CAS  Google Scholar 

  • Yamamoto K, Sokabe T, Watabe T, Miyazono K, Yamashita JK, Obi S, Ohura N, Matsushita A, Kamiya A, Ando J (2005) Fluid shear stress induces differentiation of Flk-1-positive embryonic stem cells into vascular endothelial cells in vitro. Am J Physiol Heart Circ Physiol 288:H1915–H1924

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was carried out in the Department of Physiology Research Center and Aerospace Dynamics Laboratory, the Fourth Military Medical University, People's Republic of China. This study was supported by a National Nature Science Foundation of China Grant (30973808).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Jing Ma or Zongren Wang.

Additional information

Communicated by: Sven Thatje

Xiaofeng Zhang, Yayun Nan, and Huan Wang contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, X., Nan, Y., Wang, H. et al. Model microgravity enhances endothelium differentiation of mesenchymal stem cells. Naturwissenschaften 100, 125–133 (2013). https://doi.org/10.1007/s00114-012-1002-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00114-012-1002-5

Keywords

Navigation