Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, West Huaihai Road, Xuzhou, 221002, Jiangsu, People's Republic of China.
Cell Biochem Biophys. 2013;67(3):1181-91. doi: 10.1007/s12013-013-9632-6.
The efficiency of the intravascular delivery of mesenchymal stem cells (MSCs) homing to bone marrow has been largely limited. This study aimed to evaluate the homing efficacy in irradiated mice of MSCs that have been engineered to overexpress the murine Cxcr4 gene. Mouse MSCs were infected by a lentivirus vector carrying Cxcr4. MSC migration was detected by an in vitro transwell migration assay. EGFP-positive MSCs were systemically injected into BALB/c mice and detected in bone marrow samples by flow cytometry. The concentration of mouse stromal-derived factor 1 was detected by ELISA. The plasma concentration of the inflammatory cytokines, interleukin (IL)-6, IL-10, MCP-1, IFN-γ, TNF-α, and IL-12p70, were determined by cytometric bead array. MSCs that overexpressed Cxcr4 displayed enhanced migration toward a stromal-derived factor 1 gradient. The transplantation of Cxcr4-overexpressing MSCs into irradiated mice leads to increased homing to the bone marrow. Moreover, the frequency of the EGFP-positive cells in a bone marrow infusion 24 h after total body irradiation was 2.2-fold more than at 4 h after irradiation. The concentration of both plasma and bone marrow stromal-derived factor 1 increased after irradiation, and this was positively correlated with the number of Cxcr4-overexpressing MSCs homing to the bone marrow. Moreover, compared with the control groups, the plasma levels of IL-6, IFN-γ, TNF-α, and MCP-1 and IL-12p70 in recipients infused with Cxcr4-overexpressing MSCs was significantly decreased. The level of IL-10 was increased, which correlated with changes in the Th1 and Th2 subset balance. MSCs that overexpressed Cxcr4 and were injected into irradiated mice had an enhanced homing capacity which was related to the bone marrow level of stromal-derived factor 1.
间充质干细胞（MSCs）归巢骨髓的血管内递送效率在很大程度上受到限制。本研究旨在评估过表达鼠 Cxcr4 基因的 MSCs 在辐照小鼠中的归巢效率。用携带 Cxcr4 的慢病毒载体感染小鼠 MSCs。通过体外 Transwell 迁移实验检测 MSC 迁移。通过流式细胞术检测 EGFP 阳性 MSC 系统注射到 BALB/c 小鼠后在骨髓样本中的归巢情况。通过 ELISA 检测鼠基质衍生因子 1 的浓度。通过细胞因子微珠阵列测定炎症细胞因子白细胞介素 (IL)-6、IL-10、MCP-1、IFN-γ、TNF-α 和 IL-12p70 的血浆浓度。过表达 Cxcr4 的 MSC 向基质衍生因子 1 梯度的迁移能力增强。将过表达 Cxcr4 的 MSC 移植到辐照小鼠中可增加向骨髓的归巢。此外，全身照射后 24 小时骨髓输注中 EGFP 阳性细胞的频率比照射后 4 小时增加了 2.2 倍。照射后血浆和骨髓基质衍生因子 1 的浓度均升高，与归巢到骨髓的 Cxcr4 过表达 MSC 数量呈正相关。此外，与对照组相比，输注过表达 Cxcr4 的 MSC 的受者血浆中 IL-6、IFN-γ、TNF-α 和 MCP-1 以及 IL-12p70 的水平明显降低，IL-10 水平升高，这与 Th1 和 Th2 亚群平衡的变化有关。过表达 Cxcr4 并注射到辐照小鼠中的 MSC 具有增强的归巢能力，这与骨髓基质衍生因子 1 水平有关。
