ABSTRACT
BACKGROUND: Mesenchymal stromal cells (MSCs) may reduce inflammation and promote tissue repair in pulmonary emphysema. AIM: To study the safety and feasibility of bone marrow-derived autologous (BM-) MSC intravenous administration to patients with severe emphysema. DESIGN: A phase I, prospective open-label study registered at ClinicalTrials.gov as NCT01306513 Eligible patients had lung volume reduction surgery (LVRS) on two separate occasions. During the first LVRS bone marrow was collected, from which MSCs were isolated and expanded ex vivo After 8 weeks, patients received two autologous MSC infusions 1 week apart, followed by the second LVRS procedure at 3 weeks after the second BM-MSC infusion. METHODS: Up to 3 weeks after the last MSC infusion adverse events were recorded. Using immunohistochemistry and qPCR for analysis of cell and proliferation markers, emphysematous lung tissue obtained during the first surgery was compared with lung tissue obtained after the second surgical session to assess BM-MSC effects. RESULTS: From 10 included patients three were excluded: two did not receive MSCs due to insufficient MSC culture expansion, and one had no second surgery. No adverse events related to MSC infusions occurred and lung tissue showed no fibrotic responses. After LVRS and MSC infusions alveolar septa showed a 3-fold increased expression of the endothelial marker CD31 (P = 0.016). CONCLUSIONS: Autologous MSC treatment in severe emphysema is feasible and safe. The increase in CD31 expression after LVRS and MSC treatment suggests responsiveness of microvascular endothelial cells in the most severely affected parts of the lung.
Subject(s)
Mesenchymal Stem Cell Transplantation/methods , Pulmonary Emphysema/therapy , Stromal Cells/transplantation , Adult , Aged , Bone Marrow Cells/cytology , Cell Proliferation , Endothelial Cells/cytology , Endothelial Cells/metabolism , Female , Follow-Up Studies , Humans , Immunohistochemistry , Lung/blood supply , Lung/surgery , Male , Middle Aged , Neovascularization, Physiologic , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Pneumonectomy , Prospective Studies , Pulmonary Emphysema/pathology , Pulmonary Emphysema/physiopathology , Severity of Illness Index , Transplantation, Autologous , Treatment OutcomeABSTRACT
BACKGROUND: Thus far, four soy allergens have been characterized. Their diagnostic value was assessed only using a case-control design with controls not suspected of soy allergy or in a soy-allergic population without controls. Our objective was to analyze the diagnostic value of specific immunoglobulin E (sIgE) to Gly m 2S albumin, Gly m 4, 5, and 6, and their possible relation with severity or culprit soy product. METHODS: Adult patients suspected of soy allergy were included (n = 46). Allergy was confirmed by challenge (n = 19) or history (n = 16) and excluded by challenge in 11 patients. Soy components were analyzed by ImmunoCAP. Diagnostic value was assessed in the challenged patient group by an area under receiver operating characteristic (ROC) curve (AUC). RESULTS: Specific immunoglobulin E to Gly m 2S albumin had the highest AUC (0.79), comparable to skin prick test (SPT) and sIgE to soy extract (0.76 and 0.77, respectively). All patients were sensitized to either soy extract or Gly m 4 (sIgE ≥ 0.35 kU/l). sIgE to soy extract, Gly m 5, and Gly m 6 was significantly higher in patients with mild symptoms (P = 0.04, 0.02 and 0.02, respectively). Patients only reacting to soy milk had higher sIgE levels to Gly m 4 (median 9.8 vs 1.1 kU/l, P = 0.01). CONCLUSION: Specific immunoglobulin E to Gly m 2S albumin had the best accuracy in diagnosing soy allergy. Gly m 5 and 6 were related to mild symptoms. Higher levels of Gly m 4 were related to allergy to soy milk.
