SDF-1/CXCR4 axis modulates bone marrow mesenchymal stem cell apoptosis, migration and cytokine secretion

• Published in: Protein & cell 2011-10, Vol.2 (10), p.845-854
• Main Authors: Liu, Xiaolei, Duan, Biyan, Cheng, Zhaokang, Jia, Xiaohua, Mao, Lina, Fu, Hao, Che, Yongzhe, Ou, Lailiang, Liu, Lin, Kong, Deling
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Biochemistry; Biomedical and Life Sciences; Bone Marrow Cells - metabolism; Bone Marrow Cells - physiology; Bone Marrow Cells - secretion; Cell Biology; Cell Hypoxia; Cell Movement; Chemokine CXCL12 - genetics; Chemokine CXCL12 - pharmacology; Chemokine CXCL12 - physiology; Cytokines - secretion; Developmental Biology; Gene Expression; Human Genetics; L-Lactate Dehydrogenase - metabolism; Life Sciences; Male; MAP Kinase Signaling System; Mesenchymal Stromal Cells - metabolism; Mesenchymal Stromal Cells - physiology; Mesenchymal Stromal Cells - secretion; Protein Science; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; Receptors, CXCR4 - metabolism; Research Article; Stem Cells
• ISSN: 1674-800X; 1674-8018
• DOI: 10.1007/s13238-011-1097-z

Bone marrow mesenchymal stem cells (MSCs) are considered as a promising cell source to treat the acute myocardial infarction. However, over 90% of the stem cells usually die in the first three days of transplantation. Survival potential, migration ability and paracrine capacity have been considered as the most important three factors for cell transplantation in the ischemic cardiac treatment. We hypothesized that stromal-derived factor-1 (SDF-1)/CXCR4 axis plays a critical role in the regulation of these processes. In this study, apoptosis was induced by exposure of MSCs to H 2 O 2 for 2 h. After re-oxygenation, the SDF-1 pretreated MSCs demonstrated a significant increase in survival and proliferation. SDF-1 pretreatment also enhanced the migration and increased the secretion of pro-survival and angiogenic cytokines including basic fibroblast growth factor and vascular endothelial growth factor. Western blot and RT-PCR demonstrated that SDF-1 pretreatment significantly activated the pro-survival Akt and Erk signaling pathways and up-regulated Bcl-2/Bax ratio. These protective effects were partially inhibited by AMD3100, an antagonist of CXCR4.We conclude that the SDF-1/CXCR4 axis is critical for MSC survival, migration and cytokine secretion.