Autologous mesenchymal stem cell transplantation induces angiogenesis in rat ischemic limbs Significance of monocyte chemoattractant protein-1 changes in plasma and ischemic tissues / 中国组织工程研究

ABSTRACT

OBJECTIVE: To observe monocyte chemoattractant protein 1 (MCP-1) changes in ischemic tissue during the process of angiogenesis induction in ischemic limbs by autologous mesenchymal stem cell (MSC) transplantation.METHODS: Twenty male Sprague-Dawley rats were randomized to 2 groups (n = 10): model and MSC transplantation. Femoral and tibial bone marrow was taken to isolate and culture MSCs by percoll density gradient method. Cells of the 3~(rd) or 4~(th) passage were used for transplantation. Severe bilateral hind limb ischemia was surgically created in each group rats. Two hours after model establishment, MSCs (1×10~(11)/L) were infused into the ischemic region of rats from the MSC transplantation group, and the model group received the same amount of phosphate buffered saline. Collateral artery formation was determined by angiographic analysis and histological assessment. CD68~+ macrophage infiltration was examined by immunohistochemistry. MCP-1 protein expression in the plasma and ischemic tissue was detected by enzyme-linked immunosorbent assay. MCP-1 mRNA expression in ischemic tissue was detected by reverse transcription-polymerase chain reaction.RESULTS: At postoperative 28 days, treatment with MSC transplantation lead to collateral vessel formation, and immunohistochemistry demonstrated that CD68~+ macrophage infiltration was lower compared with the model group. MCP-1 protein and mRNA expression in the plasma and ischemia tissue was significantly lower in the MSC transplantation group than in the model group (P < 0.05).CONCLUSION: Following MSC transplantation, MCP-1 may play an important role in ischemia-induced angiogenesis. This indicates that MCP-1 would become one possible target molecule for modulating inflammatory angiogenesis by MSC Transplantation.