title: TNF-α increases bone marrow mesenchymal stem cell migration to ischemic tissues.
abstract: The objective of this study was to analyze the influence of TNF-α on rat mesenchymal stem cells (MSCs) and to assess feasibility of MSC transplantation to repair ischemic injury. In this study, adhesion molecules and cell specific surface markers on MSCs were measured after exposure to different concentrations of TNF-α. MSCs stimulated with varying concentrations of TNF-α were cultured with aortic endothelial cells, and the adhesion rate was measured. MSCs were then stimulated with an optimum concentration of TNF-α as determined in vitro, and injected intravenously into rats with ischemic hind limb injury. The number of MSCs in muscle samples from the ischemic area was counted. The results showed that (1) TNF-α induced a concentration-dependent increase in VCAM-1 expression in MSCs, whereas the expression of L-selectin, ICAM-1 and VLA-4 did not change significantly. Expression of MSC-specific antigens was unchanged. (2) MSCs pretreated with 10 ng/ml TNF-α showed significantly increased adhesion to endothelial cells in vitro, and accumulated to a greater extent in the areas of ischemic damage in rat hind limbs. We were able to conclude that TNF-α has no effect on expression of MSC-specific markers, but can increase the expression of VCAM-1 on rat MSCs. Suitable concentrations of TNF-α can promote MSC adhesion to endothelial cells and migration to damaged tissue.
authors.affiliation: Institute of Anatomy & Histology and Embryology, Medical School of Shandong University, Jinan 250012, Shandong, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Xiao
authors.forename: Shi-kun
authors.initials: SK
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Tian
authors.forename: Li
authors.initials: L
authors.lastname: Xin
authors.forename: Zhi-geng
authors.initials: ZG
authors.lastname: Zou
authors.forename: Yan-lai
authors.initials: YL
authors.lastname: Hu
authors.forename: Cui-ming
authors.initials: CM
authors.lastname: Chang
authors.forename: Xue-ying
authors.initials: XY
authors.lastname: Wang
authors.forename: Qun-sheng
authors.initials: QS
authors.lastname: Yin
authors.forename: Xiang-hong
authors.initials: XH
authors.lastname: Zhang
authors.forename: Li-yan
authors.initials: LY
authors.lastname: Wang
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D039041:Integrin alpha4beta1 / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007511:Ischemia / Q000628:therapy*; D019041:L-Selectin / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D039041:Integrin alpha4beta1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin