Fibrocytes mediate intimal hyperplasia post-vascular injury and are regulated by two tissue factor-dependent mechanisms.

BACKGROUND: CD34(+) α-smooth muscle actin (SMA)(+) cells mediate intimal hyperplasia (IH) after mechanical endoluminal injury. We previously found that IH is tissue factor (TF) dependent. The precise phenotype of the CD34(+) cells mediating IH is unknown and the mechanisms of TF are also unknown. OBJECTIVE: To define the phenotype of cells mediating IH and compare the effects of inhibiting TF on different subsets of CD34(+) cells. METHODS: Endoluminal injury was induced in C57BL/6 and two strains of mice expressing a human tissue factor pathway inhibitor (hTFPI) fusion protein on different subsets of CD34(+) cells. Confocal microscopy, immunocytofluorescence and real-time PCR were used to determine phenotype. RESULTS: Neointimal cells in C57BL/6 mice were defined as a subset of fibrocytes (CD34(+) CD45(+) collagen-1(+) ) expressing SMA, CD31, TIE-2, CXCR4 and CXCL12. Similar cells circulated post-injury and were also found in mice expressing hTFPI on CD34(+) CD31(+) cells, though in these mice, hTFPI inhibited CD31(+) fibrocyte hyperplasia, so no IH developed. Mice with hTFPI on all CD34(+) α-SMA(+) cells repaired arteries back to a pre-injured state. No CD31(+) fibrocytes were found in these mice unless an anti-hTFPI antibody was administered. Similar findings in protease activated receptor (PAR)-1-deficient mice suggested hTFPI prevented thrombin signaling through PAR-1. In vitro, thrombin increased the number of CD31(+) fibrocytes. CONCLUSIONS: Inhibition of TF on CD31(+) fibrocytes inhibits IH whereas inhibition on all CD34(+) α-SMA(+) cells (or PAR-1 deficiency) inhibits the appearance of CD31(+) fibrocytes and promotes repair. These data enhance our understanding of IH and suggest novel ways to promote regenerative repair.

Comparison of plateletpheresis with a standard and an improved collection device.

A blood cell separator with a specialized separation chamber ([TNX-6]CS-3000 Plus) was developed for the collection of platelet concentrates with higher platelet yields and lower white cell contamination than obtained with the standard blood cell separator (CS-3000). To compare these devices, normal donors were scheduled for paired plateletpheresis procedures spaced 4 weeks apart, with one procedure using the CS-3000 Plus and the other using the CS-3000. Overall, the platelet yield per unit (mean +/- SEM) was 4.3 +/- 0.1 x 10(11) with the CS-3000 Plus versus 3.7 +/- 0.1 x 10(11) with the CS-3000 (p < 0.001), and the white cell contamination per unit (mean +/- SEM) with the former was 2.4 +/- 0.7 x 10(6) versus 84.1 +/- 21.1 x 10(6) with the latter (p < 0.001). The sequence of procedures (i.e., the order in which the devices were paired) was selected randomly, and similar results were found regardless of sequence. When donors with predonation platelet counts of > or = 200 x 10(9) per L (n = 21) were studied separately, 76 percent of the collections by the CS-3000 Plus contained > or = 4 x 10(11) platelets versus 34 percent of those by the CS-3000 (p < 0.01), and 93 percent of the collections by the former contained < 5 x 10(6) white cells (69% contained < 1 x 10(6)) versus 0 percent of those by the latter (p < 0.01). Thus, platelet collections with the TNX-6 chamber consistently demonstrated high platelet yields and strikingly low white cell contamination--qualities that justify converting standard devices to devices with a TNX-6 chamber.