Intravenous MSCs embolize to lung and improve myocardial infarcts in mice by activation to express the anti‐inflammatory protein TSG‐6

Abstract

Improved assays for human DNA and mRNA were used to examine the paradox that intravenously infused human multipotent stromal cells (hMSCs) enhance tissue repair with limited engraftment. After 106 hMSCs were intravenously infused into mice, most of the cells were trapped as emboli in the lung. The cells in the lung gradually disappeared with a half‐life of about 24 hr but less than 2,000 cells appeared in other tissues. The hMSCs in lung up‐regulated expression of multiple genes with the largest increase in the anti‐inflammatory protein TSG‐6. After myocardial infarction, intravenous hMSCs or recombinant TSG‐6 decreased activities of serum plasmin and heart MMP‐9. Infusion of MSCs but not MSCs with a knock down of TSG‐6 reduced infarct size. The results suggest improvements seen in other animal models and patients after infusions of MSCs are at least in part explained by activation of MSCs to secrete TSG‐6. Supported in part by NIH grants HL 073755, P40 RR 17447, and P01 HL 075161