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Enhanced Healing of Rat Calvarial Bone Defects with Hypoxic Conditioned Medium from Mesenchymal Stem Cells through Increased Endogenous Stem Cell Migration via Regulation of ICAM-1 Targeted-microRNA-221

  • Chang, Woochul (Department of Biology Education, College of Education, Pusan National University) ;
  • Kim, Ran (Department of Biology Education, College of Education, Pusan National University) ;
  • Park, Sang In (Institute of Catholic Integrative Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, College of Medicine) ;
  • Jung, Yu Jin (EIT/LOFUS Research Center, International St. Mary's Hospital, Catholic Kwandong University) ;
  • Ham, Onju (Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine) ;
  • Lee, Jihyun (Department of Biology Education, College of Education, Pusan National University) ;
  • Kim, Ji Hyeong (Department of Biology Education, College of Education, Pusan National University) ;
  • Oh, Sekyung (Department of Neurology and Neurological Sciences, Stanford University School of Medicine) ;
  • Lee, Min Young (Department of Molecular Physiology, College of Pharmacy, Kyungpook National University) ;
  • Kim, Jongmin (Department of Life Systems, Sookmyung Women's University) ;
  • Park, Moon-Seo (Department of Biology Education, College of Education, Pusan National University) ;
  • Chung, Yong-An (Institute of Catholic Integrative Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, College of Medicine) ;
  • Hwang, Ki-Chul (Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University) ;
  • Maeng, Lee-So (Institute of Catholic Integrative Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, College of Medicine)
  • 투고 : 2015.02.23
  • 심사 : 2015.04.24
  • 발행 : 2015.07.31

초록

The use of conditioned medium from mesenchymal stem cells may be a feasible approach for regeneration of bone defects through secretion of various components of mesenchymal stem cells such as cytokines, chemokines, and growth factors. Mesenchymal stem cells secrete and accumulate multiple factors in conditioned medium under specific physiological conditions. In this study, we investigated whether the conditioned medium collected under hypoxic condition could effectively influence bone regeneration through enhanced migration and adhesion of endogenous mesenchymal stem cells. Cell migration and adhesion abilities were increased through overexpression of intercellular adhesion molecule-1 in hypoxic conditioned medium treated group. Intercellular adhesion molecule-1 was upregulated by microRNA-221 in mesenchymal stem cells because microRNAs are key regulators of various biological functions via gene expression. To investigate the effects in vivo, evaluation of bone regeneration by computed tomography and histological assays revealed that osteogenesis was enhanced in the hypoxic conditioned medium group relative to the other groups. These results suggest that behavioral changes of endogenous mesenchymal stem cells through microRNA-221 targeted-intercellular adhesion molecule-1 expression under hypoxic conditions may be a potential treatment for patients with bone defects.

키워드

참고문헌

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