Effect of erythropoietin on mesenchymal stem cell differentiation and secretion in vitro in an acute kidney injury microenvironment

• Published in: Genetics and molecular research 2013-02, Vol.12 (4), p.6477-6487
• Main Authors: Liu, N M, Tian, J, Wang, W W, Han, G F, Cheng, J, Huang, J, Zhang, J Y
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - drug therapy; Animals; Antigens, CD34 - biosynthesis; Bone Marrow Cells - metabolism; Bone Morphogenetic Protein 7 - analysis; Cell Differentiation - drug effects; Cells, Cultured; Erythropoietin - pharmacology; Hepatocyte Growth Factor - analysis; Hyaluronan Receptors - biosynthesis; Integrin beta1 - biosynthesis; Keratin-18 - biosynthesis; Leukocyte Common Antigens - biosynthesis; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - metabolism; Mice; Mice, Inbred C57BL; Reperfusion Injury - drug therapy; Vascular Endothelial Growth Factor A - analysis
• ISSN: 1676-5680; 1676-5680
• DOI: 10.4238/2013.February.28.14

We investigated the effect of erythropoietin (EPO) on differentiation and secretion of bone marrow-derived mesenchymal stem cells in an acute kidney injury microenvironment. Acute kidney injury mouse models were prepared. Both renal cortices were then immediately collected to produce the ischemia/reperfusion kidney homogenate supernatant. The morphological and ultrastructural changes in the cells were observed using an inverted microscope and a transmission electron microscope. Cytokeratin-18 was detected using flow cytometry. Bone morphogenetic protein-7 levels, hepatocyte growth factor, and vascular endothelial growth factor in the culture medium were detected using an enzyme-linked immunosorbent assay. The cells had high CD29 and CD44 expression, as well as low CD34 and CD45 expression. More round and oval cells with cobble-like appearances were observed after EPO treatment. In addition, an increase in the number of rough endoplasmic reticula, lysosomes, and mitochondria was observed in the cytoplasm; the intercellular junction peculiar to epithelial cells was also seen on the cell surface. After treatment with ischemia/reperfusion kidney homogenate supernatant, cytokeratin-18 expression increased significantly and EPO could magnify its expression. Bone morphogenetic protein-7 levels, hepatocyte growth factor, and vascular endothelial growth factor levels after treatment with ischemia/reperfusion kidney homogenate supernatant significantly decreased, whereas EPO increased the cytokine secretion. The acute kidney injury microenvironment can induce the bone marrow-derived mesenchymal stem cells to partially differentiate into renal tubular epithelium-shaped cells, but weaken their secretion function. EPO intervention can boost up their differentiation function and reverse their low secretion effect.