Human mesenchymal stromal cells (MSCs) reduce neointimal hyperplasia in a mouse model of flow-restriction by transient suppression of anti-inflammatory cytokines

Aim: Mesenchymal stromal cells from human bone marrow (hMSCs) were observed to produce therapeutic benefits in some models for cardiac and vascular injuries but their mode of action was not defined. We tested the effects of hMSCs in models for restricted vascular flow. Methods: We made model for restricted vascular flow produced by permanent ligation of a carotid artery and injected hMSCs to clarify the effects of hMSCs to vascular lesions. Results: Seven, 14, and 28 days after infusion of hMSCs into the cardiac left ventricle of the mice, there was a significant reduction in neointimal hyperplasia (p<0.05). Seven days after administration of the hMSCs, macrophages infiltration into the ligated artery and serum levels of monocyte chemoattractive protein-1 (MCP-1/CCL-2) (p<0.05) were reduced. However, no hMSCs were detected in the lesions by sensitive PCR assays. We then observed that the serum level of MCP-1 was a potential biomarker for the therapeutic effects of hMSCs in a mouse model for high-fat-diet. Conclusions: These results indicated the administration of hMSCs decreased the initial and excess inflammatory responses to carotid artery ligation. The decrease in inflammatory response apparently decreased the subsequent neointimal hyperplasia.