diabetic impairment of c-kit+ bone marrow stem cells involves the disorders of inflammatory factors, cell adhesion and extracellular matrix molecules糖尿病损伤c - kit +骨髓干细胞涉及炎性因子的紊乱,细胞粘附和细胞外基质分子.pdfVIP

Diabetic Impairment of C-Kit+ Bone Marrow Stem Cells Involves the Disorders of Inflammatory Factors, Cell Adhesion and Extracellular Matrix Molecules 1,2 2 2 2 2 Tao-Sheng Li *, Satoshi Ikeda , Masayuki Kubo , Mako Ohshima , Hiroshi Kurazumi , Yoshihiro 2 2 2 Takemoto , Kazuhiro Ueda , Kimikazu Hamano 1 Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan, 2 Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan Abstract Bone marrow stem cells from diabetes mellitus patients exhibit functional impairment, but the relative molecular mechanisms responsible for this impairment are poorly understood. We investigated the mechanisms responsible for diabetes-related functional impairment of bone marrow stem cells by extensively screening the expression levels of inflammatory factors, cell cycle regulating molecules, extracellular matrix molecules and adhesion molecules. Bone marrow cells were collected from type 2 diabetic (db/db) and healthy control (db/m+) mice, and c-kit+ stem cells were purified (purity.85%) for experiments. Compared with the healthy control mice, diabetic mice had significantly fewer c-kit+ stem cells, and these cells had a lower potency of endothelial differentiation; however, the production of the angiogenic growth factor VEGF did not differ between groups. A pathway-focused array showed that the c-kit+ stem cells from diabetic mice had up-regulated expression levels of many inflammatory factors, in