jnrs Journal of New Results in Science 1304-7981 Tokat Gaziosmanpasa University Age-related Changes in Adhesive Phenotype of Bone Marrow-derived Mesenchymal Stem Cells on Extracellular Matrix Proteins Hrıstova-panusheva Kamelia Keremıdarska-markova Milena Altankov George Krasteva Natalia 03 02 2017 6 1 11 19 06 02 2017 02 14 2017 Copyright © 2012, Journal of New Results in Science 2012 Journal of New Results in Science

Mesenchymal stemcells (MSCs) are a promising cell source for cell-based therapies because oftheir self-renewal and multi-lineage differentiation potential. Unlikeembryonic stem cells adult stem cells are subject of aging processes and theconcomitant decline in their function. Age-related changes in MSCs have to bewell understood in order to develop clinical techniques and therapeutics basedon these cells. In  this work we havestudied the effect of aging on adhesive behaviour of bone marrow-derived MSCand MG- 63 osteoblastic cells onto three extracellular matrix proteins:fibronectin (FN), vitronectin (VN) and collagen I (Coll I). The results revealed substantial differences in adhesivebehaviour of both cell types during 21 days in culture. Bone-marrow derivedMSCs decreased significantly their adhesive affinity to all studied proteinsafter 7th day in culture with further incubation. In contrast, MG-63 cells,demonstrated a stable cell adhesive phenotype with high affinity to FN and CollI and low affinity to vitronectin over the whole culture period. These datasuggest that adhesive behaviour of MSCs to matrix proteins is affected by agingprocesses unlike MG-63 cells and the age-related changes have to be consideredwhen expanding adult stem cells for clinical applications.

 cell morphology cell attachment and spreading fibronectin vitronectin collagen I Antia, M., Baneyx, G, Kubow, K., Vogel, V., 2008. Fibronectin in aging extracellular matrix fibrils is progressively unfolded by cells and elicits an enhanced rigidity response. Farady Discuss. 139, 229 Arnesen, S., Lawson, M., 2006. Age-related changes in focal adhesions lead to altered cell behavior in tendon fibroblasts. Mech Ageing Dev. 127, 726 Banfi, A., Muraglia, A., Dozin, B., Mastrogiacomo, M., Cancedda, R., Quarto, R., 2000. Proliferation kinetics and differentiation potential of ex vivo expanded human bone marrow stromal cells: implications for their use in cell therapy. Exp. Hematol. 28, 707 Baxter, M., Wynn, R., Jowitt, S., Wraith, J., Fairbairn, L., Bellantuono, I., 2004. Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion. Stem Cells 22, 675 Bianco, P., Riminucci, M., Gronthos S., Robey P., 2001. Bone Marrow Stromal Stem Cells: Nature, Biology, and Potential Applications. Stem Cells. 19, 180 Campisi, J., Kim, S., Lim, C., 2001. Cellular senescence, cancer and aging: the telomere connection. Experimental Gerontology. 36(10), 1619 Clover J. and Gowen M., 1994. Are MG-63 and HOS TE85 Human Osteosarcoma Cell Lines Representative Models of the Osteoblastic Phenotype? Bone. 15 (6), 585 D’Ippolito, G., Schiller, P., Ricordi, C., Roos, B., Howard, G., 1999. Age-related osteogenic potential of mesenchymal stromal cells from human bone marrow, J Bone Miner Res. 14, 1115 Docheva, D., Popov, C., Mutschler, W., Schieker, M., 2007. Human mesenchymal stem cells in contact with their environment: surface characteristics and the integrin system. J Cell Mol Med. 11(1), 21 Flickinger, K.S., Carter, W.G., Culp, L. A., 1992. Deficiency in integrin-mediated transmembrane signaling and microfilament stress fiber formation by aging dermal fibroblasts from normal and down's syndrome patients. Experimental Cell Research. 203(2), 466 Gao, Y., Kostrominova, T., Faulkner, J., Wineman, A., 2008. Age related changes in mechanical properties of the epimysium in skeletal muscles of rats. J Biomech. 41, 465 Gershlak, J., Resnikoff, J., Sullivan, K., Williams, C., Wang, R., Black 3rd., L., 2013. Mesenchymal stem cells ability to generate traction stress in response to substrate stiffness is modulated by the changing extracellular matrix composition of the heart during development, Biochem Biophys Res Commun. 439, 161 Ghasroldasht, M., Irfan-Maqsood, M., Matin, M., Bidkhori, H., Naderi-Meshkin, H., Moradi, A., Bahrami, A., 2014. Mesenchymal stem cell based therapy for osteo-diseases. Cell Biol Int. 9999, 1 Hu, Q., Moerman, E., Goldstein, S., 1996. Altered expression and regulation of the alpha5beta1 integrin- fibronectin receptor lead to reduced amounts of functional alpha5beta1 heterodimer on the plasma membrane of senescent human diploid fibroblasts, Exp. Cell. Res. 224, 251 Hwang, E., Yoon, G., Kang, H., 2009. A comparative analysis of the cell biology of senescence and aging, Cell. Mol. Life Sci. 66, 2503 Hwang, E., Ok, J., Song, S., 2016. Chemical and Physical Approaches to Extend the Replicative and Differentiation Potential of Stem Cells. Stem Cell Rev. 12(3), 315 Jones, E. and McGonagle, D., 2008. Human bone marrow mesenchymal stem cells in vivo. Rheumatology. 47, 126 Keremidarska, M., Hristova, K., Hikov, T., Radeva, E., Mitev, D., Tsvetanov, I., Presker, R., Drobne, D., Drašler, B., Novak, S., Kononenko, V., Eleršič, K., Pramatarova, L.,and Krasteva, N., 2015. Development of Polymer/Nanodiamond Composite Coatings to Control Cell Adhesion, Growth, and Functions. Advances in Planar Lipid Bilayers and Liposomes. 21, Elsevier Inc., 1-26 Kim, M., Kim, C., Choi, Y., Kim, M., Park, C., Suh, Y., 2012. Age related alterations in mesenchymal stem cells related to shift in differentiation from osteogenic to adipogenic potential: implications to age associated bone diseases and defects. Mech Ageing Dev. 133, 215 Kuo, T., Hung, S., Chuang, C., Chen, C., Shih, Y., Fang, S., Yang, V., Lee, O., 2008. Stem cell therapy for liver disease: parameters governing the success of using bone marrow mesenchymal stem cells. Gastroenterology. 134, 2111 Larrick, J., Larrick J. and Mendelsohn, A., 2016. Reversal of Aged Muscle Stem Cell Dysfunction. Rejuvenation Research. 19 (5), 423 Li, L. and Xie, T., 2005. Stem cell niche: structure and functio. Annu Rev Cell Dev Biol. 21, 605 Lynch, K. and Pei, M. 2014. Age associated communication between cells and matrix: a potential impact on stem cell-based tissue regeneration strategies. Organogenesis. 10(3), 289 Mauney, J., Kaplan, D., Volloch, V., 2004. Matrix-mediated retention of osteogenic differentiation potential by human adult bone marrow stromal cells during ex vivo expansion. Biomaterials. 25, 3233 Meunier, P., Aaron, J., Edouard, C., Vignon, G., 1971. Osteoporosis and the replacement of cell populations of the marrow by adipose tissue. A quantitative study of 84 iliac bone biopsies. Clin. Orthop. Relat. Res. 80, 147 Miura, Y., 2016. Human bone marrow mesenchymal stromal/stem cells: current clinical applications and potential for hematology. International Journal of Hematology. 103(2), 122 Moursi, A., Globus, R. and Damsky, C., 1997. Interactions between integrin receptors and fibronectin are required for calvarial osteoblast differentiation in vitro. Journal of Cell Science. 110, 2187 Murdoch, A., Grady, L., Ablett, M., Katopodi, T., Meadows R. and Hardingham, T., 2007. Chondrogenic Differentiation of Human Bone Marrow Stem Cells in Transwell Cultures: Generation of Scaffold- Free Cartilage. Stem Cells. 25, 2786 Nakamizo, A., Marini, F., Amano, T., Khan, A., Studeny, M., Gumin, J., Chen, J., Hentschel, S., Vecil, G., Dembinski, J., Andreeff, M., Lang, F.F., 2005. Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Res. 65, 3307 Peister, A., Mellad, J., Larson, B., Hall, B., Gibson, L. and Prockop, D., 2004. Adult stem cells from bone marrow (MSCs) isolated from different strains of inbred mice vary in surface epitopes, rates of proliferation and differentiation potential. Blood. 103 (5), 1662 Roncoroni, L.P., Maerz, J.K., Angres, B., Steuer, H., Benz, K., Abruzzese, T., Hart, M., Rolauffs, B., Klein, G., Stoll, D. and Aicher, W., 2013. Adhesion to Extracellular Matrix Proteins can Differentiate between Human Bone Marrow Derived Mesenchymal Stem Cells and Fibroblasts. J Tissue Sci Eng S. 11, 008 Sell, D., and Monnier, V., 1989. Structure elucidation of a senescence cross-link from human extracellular matrix. Implication of pentoses in the aging process. J Biol Chem. 264(36), 21597 Sethe, S., Scutt, A., Stolzing, A., 2006. Aging of mesenchymal stem cells. Ageing Res Rev. 5(1), 91 Somaiah, C., Kumar, A., Mawrie, D., Sharma, A., Patil, S.D., Bhattacharyya, J., Swaminathan, R., Jaganathan, B., 2015. Collagen Promotes Higher Adhesion, Survival and Proliferation of Mesenchymal Stem Cells. PLoS ONE 10(12) e0145068. Stein, G., Lian, J. and Owen, T., 1990. Relationship of cell growth to the regulation of tissue-specific gene expression during osteoblast differentiation. FASEB J. 4, 3111 Tottey, S., Johnson, S., Crapo, P., Reing, J., Zhang, L., Jiang, H., Medberry, C., Reines, B., Badylak, S., 2011. The effect of source animal age upon extracellular matrix scaffold properties. Biomaterials. 32, 128 Tuan, R., Boland, G. and Tuli, R., 2003. Adult mesenchymal stem cells and cell-based tissue engineering, Arthriis Res Ther. 5, 32 Verfaillie, C., 2002. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 418, 41 Wagers, A., 2012. The stem cell niche in regenerative medicine. Cell Stem Cell. 10, 362 Wagner, W., Horn, P., Castoldi, M., Diehlmann, A., Bork, S., Saffrich, R., Benes, V., Blake, J., Pfister, S., Eckstein, V., Ho, A., 2008. Replicative Senescence of Mesenchymal Stem Cells: A Continuous and Organized Process. PLoS ONE. 3(5), e2213 Winnard, R., Gerstenfeld, L., Toma, C., Franceschi, R., 1995. Fibroncetin gene expression, synthesis and accumulation during in vitro differentiation of chicken osteoblasts. J. Bone Miner. Res. 10, 1969.