Autotransplantation of the Adipose Tissue-Derived Mesenchymal Stromal Cells in Therapy of Venous Stasis Ulcers.

Adipose tissue is a reliable source of mesenchymal stromal cells (MSC) for use in regenerative medicine. The aim of this pilot study was to describe the method, and assess the safety and the potential efficacy of transplantation of autologous adipose tissue-derived MSC for the treatment of chronic venous stasis ulcers. Study group consisted of 11 patients (mean age: 66.6 ± 9.5 years) with chronic venous stasis ulcers. Adipose tissue was harvested by tumescent-aspiration method. Stromal cells were separated using a dedicated closed system in a real-time bedside manner. The phenotype of cells was determined immediately after separation. Cell concentrate was implanted subcutaneously around the wound and the wound bed. All ulcers were assessed planimetrically before autotransplantation and every two weeks during the six-month follow-up. During the study all patients received standard local and general treatment. The preparation contained an average of 5.6 × 106 ± 4 × 106 cells per milliliter. The phenotype of 65-82% of transplanted cells expressed MSC markers: CD73+ CD90+ and CD34+. An improvement was observed in 75% of ulcers. The data showed highly significant negative correlation (p < 0.0001) between wound size and wound closure degree. There was no correlation of ulcer healing with other parameters evaluated, including age of the patients. No serious side effects were observed. Autotransplantation of adipose tissue stromal cells may be a safe and promising treatment method for chronic venous ulcers.

Two new cases of KIR3DP1, KIR2DL4-negative genotypes, one of which is also lacking KIR3DL2.

The killer immunoglobulin-like receptor (KIR) genes KIR2DL4, KIR3DL2, and KIR3DP1 are present in virtually all humans. KIR2DL4 encodes a receptor present on uterine and decidual natural killer (NK) cells and some peripheral blood NK cells. Its only known ligand is the human leukocyte antigen-G molecule expressed on extravillous trophoblasts, and on tissues in some diseases. KIR3DL2 binds HLA-A*03 and HLA-A*11 as well as HLA-B*27 dimers, and microbial CpG DNA. KIR3DP1 is a pseudogene. During our immunogenetic studies we found two individuals, one from Lower Silesia district in Poland, and another from Western Ukraine, who were reproducibly negative for KIR2DL4 and KIR3DP1 genes, using three different PCR systems. Both individuals displayed very similar genotypes, possessing only KIR3DL3, KIR2DL3, KIR2DP1, KIR2DS1, and probably a rare variant of KIR2DL1. The Pole had also KIR3DL2, which the Ukrainian was apparently lacking. The Lower Silesia has been populated after the Second World War by a remarkable percentage with displaced people from Western Ukraine, which might contribute to genetic similarity of the two individuals described here.

Activity of thrombin-activatable fibrinolysis inhibitor in the plasma of patients with abdominal aortic aneurysm.

Patients with abdominal aortic aneurysm (AAA) experience impaired balance between fibrinolysis and coagulation, manifested by increased prothrombotic tendency and intensified inflammatory processes. The aim of this study was to evaluate the TAFI activity level (thrombin activatable fibrinolysis inhibitor) in the plasma of AAA patients. Plasma levels of PAI-1 (plasminogen activator inhibitor type 1), urokinase-type plasminogen activator and uPAR (urokinase-type plasminogen activator receptor) were measured as markers of fibrinolytic activity. The study showed that the activity of the thrombin-activatable fibrinolysis inhibitor in the plasma of AAA patients was significantly lower than in the plasma of the control individuals (64.6 ±â€Š10.1 vs. 54.2 ±â€Š10.9%, P < 0.0001). TAFI activity positively correlated with the white blood cell count (r = 0.486, P < 0.005). The uPAR concentration in the AAA patients was statistically significantly higher than in the control group and positively correlated with TAFI activity (r = 0.409, P = 0.02). The levels of PAI-1 and D-dimers (fibrin fragments) were significantly higher in patients with AAA than in the control group (44.3 ±â€Š17.5 vs. 21.7 ±â€Š8.7 ng/ml and 1869.6 ±â€Š1490.1 vs. 181.5 ±â€Š188.6 ng/ml, respectively). Lowered activity of the fibrinolysis inhibitor TAFI may heighten the blood fibrinolytic potential in AAA patients and contribute to the development of comorbidities. Therefore, TAFI participation in AAA pathogenesis cannot be excluded.

Selected clotting factors in blood of patients with abdominal aortic aneurysms.

BACKGROUND: Tissue factor (TF), tissue factor pathway inhibitor (TFPI) and vascular endothelial growth factor A (VEGF-A) present in vascular structures take part in blood coagulation and in organ revascularisation. The concentration of thrombin-antithrombin complexes (TAT) in blood of patients with abdominal aortic aneurysms (AAA) reflects thrombin-generation. AIM: To determine the concentration of TF, TFPI, VEGF-A and TAT complexes in blood of patients with AAA and to consider if these factors after clot formation can play a role in the pathogenesis of abdominal aortic aneurysms. METHODS: Forty eight patients (43 men and 5 women) in the age of 59-80 (mean 72) years with AAA were examined. The blood was drawn in the morning to 3.2% natrium citrate in proportion 9:1. The concentration of TF, TFPI, VEGF-A and TAT complexes were measured in plasma with commercial kits using enzyme immunoassay. RESULTS: In plasma of patients with AAA the mean concentration of TF was elevated almost twice and TAT complexes were three times higher compared with controls. But the mean levels of TFPI and VEGF-A were similar as in control group. CONCLUSIONS: Increased concentrations of TF and TAT complexes indicate on high thrombin-generation, hypercoagulability and formation in abdominal aortic aneurysm of intraluminal thrombus, which can induce proteolytic processes in aortic wall.