Ongoing Geometric Remodeling of the Parent Artery After Flow-Diverter Stent Reconstruction in Cerebral Aneurysms: The Device Design Matters

Objective Configuration changes of the parent artery (PA) after flow-diverter (FD) stent reconstruction, caused by the bending force of the device, may have an additional role in aneurysm occlusion as a result of the secondary alteration of intra-aneurysmal hemodynamics related to the geometry alteration of the vessel. To determine the degree of PA deformation and aneurysm occlusion rates after deployment of 2 different types of FD. Methods Patients treated with 2 different designs of cobalt-chromium braid (48 and 64 wire braid) structure FD were subject to analysis. Vascular angle changes at the level of the reconstructed segment immediately after FD deployment and at 1 year follow-up were measured and the potential relationship with aneurysmal occlusion rate was analyzed. Results Forty-two patients harboring 48 aneurysms were included in the present study. The aneurysms were divided into side wall (85.4%) and bifurcation types (14.6%). Twenty-six aneurysms were treated using the Pipeline FD (48 wire braid; 54.2%) and 22 using the Evolve FD (64 wire braid; 45.8%). Of the 48 aneurysms, 42 (87.5%) met the primary end point of complete occlusion at 12 months. The median postdeployment angle change was 7.04°± 4.59° for the Pipeline and 5.05°± 2.49° for the Evolve, whereas the median 12 months follow-up angle change was 15.49°± 10.99° and 10.01°± 8.83°, respectively. PA angle changes were significantly higher in the bifurcation group compared with the side wall group both during procedure and at 12 months follow-up. Angle change had a statistically nonsignificant association with complete aneurysm occlusion. Conclusions PA deformation starts immediately after deployment and remodeling continues for 1 year after. Aneurysms located in the vessel bifurcation were more prone to PA straightening after FD deployment than were side wall aneurysms. Furthermore, Pipeline seemed to be more prone to inducing vascular deformation, compared with Evolve

Impaired function of bone marrow stromal cells in systemic mastocytosis

Patients with systemic mastocytosis (SM) have a wide variety of problems, including skeletal abnormalities. The disease results from a mutation of the stem cell receptor (c-kit) in mast cells and we wondered if the function of bone marrow stromal cells (BMSCs; also known as MSCs or mesenchymal stem cells) might be affected by the invasion of bone marrow by mutant mast cells. As expected, BMSCs from SM patients do not have a mutation in c-kit, but they proliferate poorly. In addition, while osteogenic differentiation of the BMSCs seems to be deficient, their adipogenic potential appears to be increased. Since the hematopoietic supportive abilities of BMSCs are also important, we also studied the engraftment in NSG mice of human CD34+ hematopoietic progenitors, after being co-cultured with BMSCs of healthy volunteers vs. BMSCs derived from patients with SM. BMSCs derived from the bone marrow of patients with SM could not support hematopoiesis to the extent that healthy BMSCs do. Finally, we performed an expression analysis and found significant differences between healthy and SM derived BMSCs in the expression of genes with a variety of functions, including the WNT signaling, ossification, and bone remodeling. We suggest that some of the symptoms associated with SM might be driven by epigenetic changes in BMSCs caused by dysfunctional mast cells in the bone marrow of the patients

Bone Marrow-Derived Mesenchymal Stromal Cells (MSCs) Modulate the Inflammatory Character of Alveolar Macrophages from Sarcoidosis Patients

Sarcoidosis is a devastating inflammatory disease affecting many organs, especially the lungs and lymph nodes. Bone marrow-derived mesenchymal stromal cells (MSCs) can “reprogram” various types of macrophages towards an anti-inflammatory phenotype. We wanted to determine whether alveolar macrophages from sarcoidosis subjects behave similarly by mounting an anti-inflammatory response when co-cultured with MSCs. Fifteen sarcoidosis and eight control subjects underwent bronchoscopy and bronchoalveolar lavage (BAL). Unselected BAL cells (70–94% macrophages) were isolated and cultured with and without MSCs from healthy adults. Following stimulation of the cultured cells with lipopolysaccharide, the medium was removed to measure interleukin 10 and tumor necrosis factor alpha (IL-10 and TNF-α). In two additional sarcoidosis subjects, flow cytometry was used to study intracellular cytokines and surface markers associated with alveolar macrophages to confirm the results. Unselected BAL cells from sarcoidosis subjects co-cultured with MSCs showed a reduction in TNF-α (pro-inflammatory M1) and an increase in IL-10 (anti-inflammatory M2) in 9 of 11 samples studied. Control subject samples showed few, if any, differences in cytokine production. Unselected BAL cells from two additional patients analyzed by flow cytometry confirmed a switch towards an anti-inflammatory state (i.e., M1 to M2) after co-culture with MSCs. These results suggest that, similarly to other macrophages, alveolar macrophages also respond to MSC contacts by changing towards an anti-inflammatory phenotype. Based on our results, we hypothesize that mesenchymal stromal cells applied to the airways might alleviate lung inflammation and decrease steroid need in patients with sarcoidosis