Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2015, Article ID 769402, 14 pages
http://dx.doi.org/10.1155/2015/769402
Research Article

Effect of Metformin on Viability, Morphology, and Ultrastructure of Mouse Bone Marrow-Derived Multipotent Mesenchymal Stromal Cells and Balb/3T3 Embryonic Fibroblast Cell Line

1Electron Microscopy Laboratory, The Faculty of Biology and Animal Science, University of Environmental and Life Sciences, Kożuchowska 5b Street, 50-631 Wroclaw, Poland
2Wrocławskie Centrum Badań EIT+, Stablowicka 147 Street, 54-066 Wroclaw, Poland
3Department of Experimental Oncology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland
4Department of Biotechnology and Food Microbiology, Faculty of Food Science University of Environmental and Life Sciences, Chelmonskiego 37/41, 51-630 Wroclaw, Poland

Received 8 January 2015; Revised 27 March 2015; Accepted 15 April 2015

Academic Editor: Wiep Scheper

Copyright © 2015 Agnieszka Śmieszek et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. L. B. A. Rojas and M. B. Gomes, “Metformin: an old but still the best treatment for type 2 diabetes,” Diabetology & Metabolic Syndrome, vol. 5, no. 1, article 6, 2013. View at Publisher · View at Google Scholar · View at Scopus
  2. T. V. Kourelis and R. D. Siegel, “Metformin and cancer: new applications for an old drug,” Medical Oncology, vol. 29, no. 2, pp. 1314–1327, 2012. View at Publisher · View at Google Scholar · View at Scopus
  3. B. Viollet, B. Guigas, N. Sanz Garcia, J. Leclerc, M. Foretz, and F. Andreelli, “Cellular and molecular mechanisms of metformin: an overview,” Clinical Science, vol. 122, no. 6, pp. 253–270, 2012. View at Publisher · View at Google Scholar · View at Scopus
  4. I. N. Alimova, B. Liu, Z. Fan et al., “Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro,” Cell Cycle, vol. 8, no. 6, pp. 909–915, 2009. View at Publisher · View at Google Scholar · View at Scopus
  5. B. Liu, Z. Fan, S. M. Edgerton et al., “Metformin induces unique biological and molecular responses in triple negative breast cancer cells,” Cell Cycle, vol. 8, no. 13, pp. 2031–2040, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. E. Giovannucci, D. M. Harlan, M. C. Archer et al., “Diabetes and cancer: a consensus report,” Diabetes Care, vol. 33, no. 7, pp. 1674–1685, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. Q. Luo, D. Hu, S. Hu, M. Yan, Z. Sun, and F. Chen, “In vitro and in vivo anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinoma,” BMC Cancer, vol. 12, article 517, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. E. Karnevi, K. Said, R. Andersson, and A. H. Rosendahl, “Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells,” BMC Cancer, vol. 13, article 235, 2013. View at Publisher · View at Google Scholar · View at Scopus
  9. W. H. Gotlieb, J. Saumet, M.-C. Beauchamp et al., “In vitro metformin anti-neoplastic activity in epithelial ovarian cancer,” Gynecologic Oncology, vol. 110, no. 2, pp. 246–250, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. N. Wu, C. Gu, H. Gu, H. Hu, Y. Han, and Q. Li, “Metformin induces apoptosis of lung cancer cells through activating JNK/p38 MAPK pathway and GADD153,” Neoplasma, vol. 58, no. 6, pp. 482–490, 2011. View at Publisher · View at Google Scholar · View at Scopus
  11. H.-P. Chen, J.-J. Shieh, C.-C. Chang et al., “Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner: population-based and in vitro studies,” Gut, vol. 62, no. 4, pp. 606–615, 2013. View at Publisher · View at Google Scholar · View at Scopus
  12. V. N. Anisimov, L. M. Berstein, I. G. Popovich et al., “If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice,” Aging, vol. 3, no. 2, pp. 148–157, 2011. View at Google Scholar · View at Scopus
  13. T. Chiba, T. Tsuchiya, T. Komatsu, R. Mori, H. Hayashi, and I. Shimokawa, “Development of calorie restriction mimetics as therapeutics for obesity, diabetes, inflammatory and neurodegenerative diseases,” Current Genomics, vol. 11, no. 8, pp. 562–567, 2010. View at Publisher · View at Google Scholar · View at Scopus
  14. S. N. Hardouin, R. Guo, P.-H. Romeo, A. Nagy, and J. E. Aubin, “Impaired mesenchymal stem cell differentiation and osteoclastogenesis in mice deficient for Igf2-P2 transcripts,” Development, vol. 138, no. 2, pp. 203–213, 2011. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Z. Ratajczak, “Igf2-H19, an imprinted tandem gene, is an important regulator of embryonic development, a guardian of proliferation of adult pluripotent stem cells, a regulator of longevity, and a ‘passkey’ to cancerogenesis,” Folia Histochemica et Cytobiologica, vol. 50, no. 2, pp. 171–179, 2012. View at Publisher · View at Google Scholar · View at Scopus
  16. C. D. Porada and G. Almeida-Porada, “Mesenchymal stem cells as therapeutics and vehicles for gene and drug delivery,” Advanced Drug Delivery Reviews, vol. 62, no. 12, pp. 1156–1166, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Scanu, L. Mancuso, and G. Cao, “Evaluation of the use of human mesenchymal stem cells for acute toxicity tests,” Toxicology in Vitro, vol. 25, no. 8, pp. 1989–1995, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. K. Marycz, J. Krzak-Roś, A. Donesz-Sikorska, and A. Śmieszek, “The morphology, proliferation rate, and population doubling time factor of adipose-derived mesenchymal stem cells cultured on to non-aqueous SiO2, TiO2, and hybrid sol-gel-derived oxide coatings,” Journal of Biomedical Materials Research A, vol. 102, no. 11, pp. 4017–4026, 2014. View at Publisher · View at Google Scholar · View at Scopus
  19. G. Wu and H. R. Schöler, “Role of Oct4 in the early embryo development,” Cell Regeneration, vol. 3, no. 1, article 7, 2014. View at Publisher · View at Google Scholar
  20. H. Ren, Y. Cao, Q. Zhao et al., “Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions,” Biochemical and Biophysical Research Communications, vol. 347, no. 1, pp. 12–21, 2006. View at Publisher · View at Google Scholar · View at Scopus
  21. P. J. Mishra, J. W. Glod, and D. Banerjee, “Mesenchymal stem cells: flip side of the coin,” Cancer Research, vol. 69, no. 4, pp. 1255–1258, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Fischer, K. Timper, T. Radimerski et al., “Metformin induces glucose uptake in human preadipocyte-derived adipocytes from various fat depots,” Diabetes, Obesity and Metabolism, vol. 12, no. 4, pp. 356–359, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. K. Marycz, A. Śmieszek, J. Grzesiak, A. Donesz-Sikorska, and J. Krzak-Roś, “Application of bone marrow and adipose-derived mesenchymal stem cells for testing the biocompatibility of metal-based biomaterials functionalized with ascorbic acid,” Biomedical Materials, vol. 8, no. 6, Article ID 065004, 2013. View at Publisher · View at Google Scholar · View at Scopus
  24. M. Maredziak, K. Marycz, A. Śmieszek, D. Lewandowski, and N. Y. Toker, “The influence of static magnetic fields on canine and equine mesenchymal stem cells derived from adipose tissue,” In Vitro Cellular and Developmental Biology—Animal, vol. 50, no. 6, pp. 562–571, 2014. View at Publisher · View at Google Scholar · View at Scopus
  25. A. Witek-Krowiak, D. Podstawczyk, K. Chojnacka, A. Dawiec, and K. Marycz, “Modelling and optimization of chromium III biosorption on soybean meal,” Central European Journal of Chemistry, vol. 11, no. 9, pp. 1505–1517, 2013. View at Publisher · View at Google Scholar · View at Scopus
  26. K. Kaliński, K. Marycz, J. Czogała, E. Serwa, and W. Janeczek, “An application of scanning electron microscopy combined with roentgen microanalysis (SEM–EDS) in canine urolithiasis,” Journal of Electron Microscopy (Tokyo), vol. 61, no. 1, pp. 47–55, 2012. View at Publisher · View at Google Scholar · View at Scopus
  27. P. Chomczynski and N. Sacchi, “Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction,” Analytical Biochemistry, vol. 162, no. 1, pp. 156–159, 1987. View at Google Scholar · View at Scopus
  28. J. A. Menendez and A. Vazquez-Martin, “Rejuvenating regeneration: metformin activates endogenous adult stem cells,” Cell Cycle, vol. 11, no. 19, pp. 3521–3522, 2012. View at Publisher · View at Google Scholar · View at Scopus
  29. P. J. Marie and O. Fromigué, “Osteogenic differentiation of human marrow-derived mesenchymal stem cells,” Regenerative Medicine, vol. 1, no. 4, pp. 539–548, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. E. Luzi, F. Marini, S. C. Sala, I. Tognarini, G. Galli, and M. L. Brandi, “Osteogenic differentiation of human adipose tissue-derived stem cells is modulated by the miR-26a targeting of the SMAD1 transcription factor,” Journal of Bone and Mineral Research, vol. 23, no. 2, pp. 287–295, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. K. Tamama, C. K. Sen, and A. Wells, “Differentiation of bone marrow mesenchymal stem cells into the smooth muscle lineage by blocking ERK/MAPK signaling pathway,” Stem Cells and Development, vol. 17, no. 5, pp. 897–908, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. L. A. Solchaga, K. J. Penick, and J. F. Welter, “Chondrogenic differentiation of bone marrow-derived mesenchymal stem cells: tips and tricks,” Methods in Molecular Biology, vol. 698, pp. 253–278, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. M. Zakikhani, R. Dowling, I. G. Fantus, N. Sonenberg, and M. Pollak, “Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells,” Cancer Research, vol. 66, no. 21, pp. 10269–10273, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. C.-F. Sum, J. M. Webster, A. B. Johnson, C. Catalano, B. G. Cooper, and R. Taylor, “The effect of intravenous metformin on glucose metabolism during hyperglycaemia in type 2 diabetes,” Diabetic Medicine, vol. 9, no. 1, pp. 61–65, 1992. View at Publisher · View at Google Scholar · View at Scopus
  35. M. Foretz, S. Hébrard, J. Leclerc et al., “Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state,” Journal of Clinical Investigation, vol. 120, no. 7, pp. 2355–2369, 2010. View at Publisher · View at Google Scholar · View at Scopus
  36. C. Wilcock and C. J. Bailey, “Accumulation of metformin by tissues of the normal and diabetic mouse,” Xenobiotica, vol. 24, no. 1, pp. 49–57, 1994. View at Publisher · View at Google Scholar · View at Scopus
  37. Y. Gao, J. Xue, X. Li, Y. Jia, and J. Hu, “Metformin regulates osteoblast and adipocyte differentiation of rat mesenchymal stem cells,” Journal of Pharmacy and Pharmacology, vol. 60, no. 12, pp. 1695–1700, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. M. S. Molinuevo, L. Schurman, A. D. McCarthy et al., “Effect of metformin on bone marrow progenitor cell differentiation: in vivo and in vitro studies,” Journal of Bone and Mineral Research, vol. 25, no. 2, pp. 211–221, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. J. Jeyabalan, B. Viollet, P. Smitham et al., “The anti-diabetic drug metformin does not affect bone mass in vivo or fracture healing,” Osteoporosis International, vol. 24, no. 10, pp. 2659–2670, 2013. View at Publisher · View at Google Scholar · View at Scopus
  40. A. S. Abu-Zaiton, “Effect of metformin on proliferation of skin derived stem cells in the case of normoxia and hypoxia,” Journal of Biological Sciences, vol. 14, no. 2, pp. 149–153, 2014. View at Publisher · View at Google Scholar · View at Scopus
  41. Z. Pincus and J. A. Theriot, “Comparison of quantitative methods for cell-shape analysis,” Journal of Microscopy, vol. 227, no. 2, pp. 140–156, 2007. View at Publisher · View at Google Scholar · View at MathSciNet · View at Scopus
  42. M. Nakamura and K. Kakudo, Molecular Mechanism and Morphology in Cancer: Foreword, Bentham eBooks, Chiba, Japan, 2009.
  43. G. Wieczorek, C. Steinhoff, R. Schulz et al., “Gene expression profile of mouse bone marrow stromal cells determined by cDNA microarray analysis,” Cell and Tissue Research, vol. 311, no. 2, pp. 227–237, 2003. View at Google Scholar · View at Scopus
  44. D. J. Holt and D. W. Grainger, “Multinucleated giant cells from fibroblast cultures,” Biomaterials, vol. 32, no. 16, pp. 3977–3987, 2011. View at Publisher · View at Google Scholar · View at Scopus
  45. T. Schilling, C. Schonefeldt, S. Zeck et al., “Local expression of insulin-like growth factor (IGF) signaling components during in vitro aging of mesenchymal stem cells,” Journal of Stem Cells & Regenerative Medicine, vol. 2, no. 1, pp. 41–42, 2007. View at Google Scholar
  46. R. L. Page, S. Ambady, W. F. Holmes et al., “Induction of stem cell gene expression in adult human fibroblasts without transgenes,” Cloning and Stem Cells, vol. 11, no. 3, pp. 417–426, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. Y. X. Fan, C. H. Gu, Y. L. Zhang et al., “Oct4 and Sox2 overexpression improves the proliferation and differentiation of bone mesenchymal stem cells in Xiaomeishan porcine,” Genetics and Molecular Research, vol. 12, no. 4, pp. 6067–6079, 2013. View at Publisher · View at Google Scholar · View at Scopus
  48. H. Obokata, T. Wakayama, Y. Sasai et al., “Stimulus-triggered fate conversion of somatic cells into pluripotency,” Nature, vol. 505, no. 7485, pp. 641–647, 2014. View at Publisher · View at Google Scholar · View at Scopus