title: 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.
abstract: 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.
authors.affiliation: Department of Biology Education, College of Education, Pusan National University, Busan 609-735, Korea.
authors.forename: Woochul
authors.initials: W
authors.lastname: Chang
authors.affiliation: Department of Biology Education, College of Education, Pusan National University, Busan 609-735, Korea.
authors.forename: Ran
authors.initials: R
authors.lastname: Kim
authors.affiliation: Institute of Catholic Integrative Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, College of Medicine, Incheon 403-720, Korea.
authors.forename: Sang In
authors.initials: SI
authors.lastname: Park
authors.affiliation: EIT/LOFUS Research Center, International St. Mary's Hospital, Catholic Kwandong University, Incheon 404-834, Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Jung
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Onju
authors.initials: O
authors.lastname: Ham
authors.affiliation: Department of Biology Education, College of Education, Pusan National University, Busan 609-735, Korea.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biology Education, College of Education, Pusan National University, Busan 609-735, Korea.
authors.forename: Ji Hyeong
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Sekyung
authors.initials: S
authors.lastname: Oh
authors.affiliation: Department of Molecular Physiology, College of Pharmacy, Kyungpook National University, Daegu 702-701, Korea.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul 140-742, Korea.
authors.forename: Jongmin
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biology Education, College of Education, Pusan National University, Busan 609-735, Korea.
authors.forename: Moon-Seo
authors.initials: MS
authors.lastname: Park
authors.affiliation: Institute of Catholic Integrative Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, College of Medicine, Incheon 403-720, Korea.
authors.forename: Yong-An
authors.initials: YA
authors.lastname: Chung
authors.affiliation: Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangwon 210-701, Korea.|Catholic Kwandong University International, St. Mary's Hospital, Incheon 404-834, Korea.
authors.forename: Ki-Chul
authors.initials: KC
authors.lastname: Hwang
authors.affiliation: Institute of Catholic Integrative Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, College of Medicine, Incheon 403-720, Korea.
authors.forename: Lee-So
authors.initials: LS
authors.lastname: Maeng
mesh_terms: D000818:Animals; D001861:Bone Regeneration; D015687:Cell Hypoxia; D002465:Cell Movement; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D035683:MicroRNAs / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing
chemical_list: D017077:Culture Media, Conditioned; C576526:MIRN221 microRNA, rat; D035683:MicroRNAs; D018799:Intercellular Adhesion Molecule-1
keywords: bone regeneration; calvarial defect model; hypoxic conditioned medium; intercellular adhesion molecule-1; mesenchymal stem cells; microRNA-221