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Long Term Exposure to Myrtucommulone-A Changes CD105 Expression and Differentiation Potential of Mesenchymal Stem Cells

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Mesenchymal stem cells (MSCs) represent a heterogeneous group of multipotent stem cells that could be found in various somatic tissues. MSCs are defined by molecular and functional features including spindle-shape morphology, adherence to plastic surfaces, expression of specific surface markers and differentiation potential to chondrocytes, adipocytes and osteocytes. The surface markers were proposed to affect the differentiation potential of MSCs by a limited number of studies. Endoglin (CD105) is defined to be a significant marker for osteogenic and chondrogenic differentiation ability of MSCs. Low CD105 expression is associated with increased osteogenic potential while high CD105 expression is correlated with strong chondrogenic potential. Myrtucommulone-A (MC-A) is an active compound with various biological effects on different cell types but its effect on MSC differentiation has not been described yet. In the present study we aimed at investigating the long-term effects of MC-A on hMSCs. MC-A-treatment reduced CD105 expression in distinct human mesenchymal stem cell (hMSC) lines and gave rise to CD105low population but did not change CD44, CD90 or CD73 expression. The decrease in CD105 expression reduced the chondrogenic potential of hMSCs subsequently while adipogenic or osteogenic differentiation was not affected dramatically. MC-A-treatment also suppressed the NF-κB p65 activation which might be responsible for the reduced chondrogenic potential. Our findings suggest that MC-A could be used to enrich CD105low hMSCs without the need for cell sorting or changing culture conditions which could be utilised in targeted differentiation studies.

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References

  1. Spencer ND, Gimble JM, Lopez MJ. Mesenchymal stromal cells: past, present, and future. Vet Surg. 2011;40:129–39.

    Article  PubMed  Google Scholar 

  2. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315–7.

    Article  PubMed  CAS  Google Scholar 

  3. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–7.

    Article  PubMed  CAS  Google Scholar 

  4. Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells—current trends and future prospective. Biosci Rep. 2015;35:e00191.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Beyth S, Borovsky Z, Mevorach D, Liebergall M, Gazit Z, Aslan H, et al. Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood. 2005;105:2214–9.

    Article  PubMed  CAS  Google Scholar 

  6. Levi B, Wan DC, Glotzbach JP, Hyun J, Januszyk M, Montoro D, et al. CD105 protein depletion enhances human adipose-derived stromal cell osteogenesis through reduction of transforming growth factor beta1 (TGF-beta1) signaling. J Biol Chem. 2011;286:39497–509.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Anderson P, Carrillo-Galvez AB, Garcia-Perez A, Cobo M, Martin F. CD105 (endoglin)-negative murine mesenchymal stromal cells define a new multipotent subpopulation with distinct differentiation and immunomodulatory capacities. PLoS ONE. 2013;8:e76979.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Qi J, Chen A, You H, Li K, Zhang D, Guo F. Proliferation and chondrogenic differentiation of CD105-positive enriched rat synovium-derived mesenchymal stem cells in three-dimensional porous scaffolds. Biomed Mater. 2011;6:015006.

    Article  PubMed  CAS  Google Scholar 

  9. Maeda S, Hayashi M, Komiya S, Imamura T, Miyazono K. Endogenous TGF-beta signaling suppresses maturation of osteoblastic mesenchymal cells. EMBO J. 2004;23:552–63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Mark P, Kleinsorge M, Gaebel R, Lux CA, Toelk A, Pittermann E, et al. Human mesenchymal stem cells display reduced expression of CD105 after culture in serum-free medium. Stem Cells Int. 2013;2013:698076.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Jiang T, Liu W, Lv X, Sun H, Zhang L, Liu Y, et al. Potent in vitro chondrogenesis of CD105 enriched human adipose-derived stem cells. Biomaterials. 2010;31:3564–71.

    Article  PubMed  CAS  Google Scholar 

  12. Muller H, Paul M, Hartmann D, Huch V, Blaesius D, Koeberle A, et al. Total synthesis of myrtucommulone A. Angew Chem Int Ed Engl. 2010;49:2045–9.

    Article  PubMed  CAS  Google Scholar 

  13. Iskender B, Izgi K, Karaca H, Canatan H. Myrtucommulone-A treatment decreases pluripotency- and multipotency-associated marker expression in bladder cancer cell line HTB-9. J Nat Med. 2015;69:543–54.

    Article  PubMed  CAS  Google Scholar 

  14. Iskender B, Izgi K, Sakalar C, Canatan H (2015) Priming hMSCs with a putative anti-cancer compound, myrtucommulone-a: a way to harness hMSC cytokine expression via modulating PI3K/Akt pathway? Tumour Biol. 2016;37:1967–81.

    Article  PubMed  CAS  Google Scholar 

  15. Solchaga LA, Penick KJ, Welter JF. Chondrogenic differentiation of bone marrow-derived mesenchymal stem cells: tips and tricks. Methods Mol Biol. 2011;698:253–78.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Shen G. The role of type X collagen in facilitating and regulating endochondral ossification of articular cartilage. Orthod Craniofac Res. 2005;8:11–7.

    Article  PubMed  CAS  Google Scholar 

  17. Wang D, Chen R, Zhong X, Fan Y, Lai W, Sun X. Levels of CD105 cells increase and cell proliferation decreases during S-phase arrest of amniotic fluid cells in long-term culture. Exp Ther Med. 2014;8:1604–10.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Shetty P, Cooper K, Viswanathan C. Comparison of proliferative and multilineage differentiation potentials of cord matrix, cord blood, and bone marrow mesenchymal stem cells. Asian J Transfus Sci. 2010;4:14–24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Torensma R, Prins HJ, Schrama E, Verwiel ET, Martens AC, Roelofs H, et al. The impact of cell source, culture methodology, culture location, and individual donors on gene expression profiles of bone marrow-derived and adipose-derived stromal cells. Stem Cells Dev. 2013;22:1086–96.

    Article  PubMed  CAS  Google Scholar 

  20. Zhu X, Shi W, Tai W, Liu F. The comparition of biological characteristics and multilineage differentiation of bone marrow and adipose derived Mesenchymal stem cells. Cell Tissue Res. 2012;350:277–87.

    Article  PubMed  CAS  Google Scholar 

  21. Ode A, Schoon J, Kurtz A, Gaetjen M, Ode JE, Geissler S, et al. CD73/5′-ecto-nucleotidase acts as a regulatory factor in osteo-/chondrogenic differentiation of mechanically stimulated mesenchymal stromal cells. Eur Cell Mater. 2013;25:37–47.

    Article  PubMed  CAS  Google Scholar 

  22. Davies OG, Cooper PR, Shelton RM, Smith AJ, Scheven BA. Isolation of adipose and bone marrow mesenchymal stem cells using CD29 and CD90 modifies their capacity for osteogenic and adipogenic differentiation. J Tissue Eng. 2015;6:2041731415592356.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Nassiri F, Cusimano MD, Scheithauer BW, Rotondo F, Fazio A, Yousef GM, et al. Endoglin (CD105): a review of its role in angiogenesis and tumor diagnosis, progression and therapy. Anticancer Res. 2011;31:2283–90.

    PubMed  CAS  Google Scholar 

  24. Jin HJ, Park SK, Oh W, Yang YS, Kim SW, Choi SJ. Down-regulation of CD105 is associated with multi-lineage differentiation in human umbilical cord blood-derived mesenchymal stem cells. Biochem Biophys Res Commun. 2009;381:676–81.

    Article  PubMed  CAS  Google Scholar 

  25. Parker WL, Goldring MB, Philip A. Endoglin is expressed on human chondrocytes and forms a heteromeric complex with betaglycan in a ligand and type II TGFbeta receptor independent manner. J Bone Miner Res. 2003;18:289–302.

    Article  PubMed  CAS  Google Scholar 

  26. Cheifetz S, Bellon T, Cales C, Vera S, Bernabeu C, Massague J, et al. Endoglin is a component of the transforming growth factor-beta receptor system in human endothelial cells. J Biol Chem. 1992;267:19027–30.

    PubMed  CAS  Google Scholar 

  27. Zhao L, Hantash BM. TGF-beta1 regulates differentiation of bone marrow mesenchymal stem cells. Vitam Horm. 2011;87:127–41.

    Article  PubMed  CAS  Google Scholar 

  28. Chang CB, Han SA, Kim EM, Lee S, Seong SC, Lee MC. Chondrogenic potentials of human synovium-derived cells sorted by specific surface markers. Osteoarthr Cartil. 2013;21:190–9.

    Article  PubMed  CAS  Google Scholar 

  29. Leyva-Leyva M, Lopez-Diaz A, Barrera L, Camacho-Morales A, Hernandez-Aguilar F, Carrillo-Casas EM, et al. Differential expression of adhesion-related proteins and MAPK pathways lead to suitable osteoblast differentiation of human mesenchymal stem cells subpopulations. Stem Cells Dev. 2015;24:2577–90.

    Article  PubMed  CAS  Google Scholar 

  30. Buhrmann C, Busch F, Shayan P, Shakibaei M. Sirtuin-1 (SIRT1) is required for promoting chondrogenic differentiation of mesenchymal stem cells. J Biol Chem. 2014;289:22048–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Buhrmann C, Mobasheri A, Matis U, Shakibaei M. Curcumin mediated suppression of nuclear factor-kappaB promotes chondrogenic differentiation of mesenchymal stem cells in a high-density co-culture microenvironment. Arthritis Res Ther. 2010;12:R127.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Caron MM, Emans PJ, Surtel DA, Cremers A, Voncken JW, Welting TJ, et al. Activation of NF-kappaB/p65 facilitates early chondrogenic differentiation during endochondral ossification. PLoS ONE. 2012;7:e33467.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

This study was supported by the grant from the The Scientific and Technological Research Council of Turkey (No. 115S042).

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Authors and Affiliations

  1. Department of Medical Biology, Faculty of Medicine, Erciyes University, 38039, Melikgazi, Kayseri, Turkey

    Halit Canatan & Banu Iskender

  2. Department of Medical Biochemistry, Faculty of Medicine, Erciyes University, 38039, Melikgazi, Kayseri, Turkey

    Kenan Izgi

  3. Betul-Ziya Eren Genome and Stem Cell Centre, Erciyes University, 38039, Melikgazi, Kayseri, Turkey

    Kenan Izgi, Halit Canatan & Banu Iskender

  4. Department of Histology and Embryology, Faculty of Medicine, Erciyes University, 38039, Melikgazi, Kayseri, Turkey

    Mehmet Fatih Sonmez

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  1. Kenan Izgi
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Correspondence to Banu Iskender.

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Izgi, K., Sonmez, M.F., Canatan, H. et al. Long Term Exposure to Myrtucommulone-A Changes CD105 Expression and Differentiation Potential of Mesenchymal Stem Cells. Tissue Eng Regen Med 14, 113–121 (2017). https://doi.org/10.1007/s13770-016-0020-3

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  • DOI: https://doi.org/10.1007/s13770-016-0020-3

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