title: Evidences for correlation between the reduced VCAM-1 expression and hyaluronan synthesis during cellular senescence of human mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) undergo cellular senescence during in vitro expansion culture, which accompanies the loss of migration and homing abilities. In this study, we analyzed expression levels of several surface markers of human MSCs at different passages of expansion culture. It has been shown that expression of vascular cell adhesion molecule-1 (VCAM-1) was most markedly decreased among the tested markers in the senescent MSCs. Interestingly the reduced VCAM-1 expression could be restored by applying hyaluronan, a major glycosaminoglycan ligand of CD44, to the culture. It was found that the hyaluronan level in extracellular and pericellular matrices was greatly reduced in the senescent MSCs, mainly due to the decreased expression of hyaluronan synthases, suggesting a correlation between the reduced VCAM-1 expression and hyaluronan synthesis. In fact, when hyaluronan synthases were knock-downed by siRNA transfection, the VCAM-1 expression was also reduced. Our results indicate that VCAM-1 expression in the senescent MSCs was down-regulated because of the reduced synthesis of hyaluronan. Thus, we suggest that hyaluronan supplementation in expansion culture of MSCs would compensate adverse effects induced by its decreased synthesis and subsequently enhance cell adhesion and migration abilities.
authors.affiliation: Integrative Omics Research Center, Korea Research Institute of Bioscience & Biotechnology, 111 Gwahangno, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Jung
authors.forename: Ohsuk
authors.initials: O
authors.lastname: Kwon
authors.forename: Ki-Sun
authors.initials: KS
authors.lastname: Kwon
authors.forename: Yee Sook
authors.initials: YS
authors.lastname: Cho
authors.forename: Sang Ki
authors.initials: SK
authors.lastname: Rhee
authors.forename: Jeong-Ki
authors.initials: JK
authors.lastname: Min
authors.forename: Doo-Byoung
authors.initials: DB
authors.lastname: Oh
mesh_terms: D002478:Cells, Cultured; D016922:Cellular Senescence; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000096:biosynthesis* / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D019010:Vascular Cell Adhesion Molecule-1; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases