title: A phase I study for intravenous autologous mesenchymal stromal cell administration to patients with severe emphysema.
abstract: BACKGROUND
  Mesenchymal stromal cells (MSCs) may reduce inflammation and promote tissue repair in pulmonary emphysema.
  
  
  OBJECTIVE
  To study the safety and feasibility of bone marrow-derived autologous (BM-) MSC intravenous administration to patients with severe emphysema.
  
  
  METHODS
  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.
authors.affiliation: From the Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands, j.stolk@lumc.nl.
authors.forename: J
authors.initials: J
authors.lastname: Stolk
authors.affiliation: From the Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Broekman
authors.affiliation: Department of Pathology, São Paulo University Medical School, São Paulo, Brazil.
authors.forename: T
authors.initials: T
authors.lastname: Mauad
authors.affiliation: Department of Immunohaematology and Blood Transfusion.
authors.forename: J J
authors.initials: JJ
authors.lastname: Zwaginga
authors.affiliation: Department of Immunohaematology and Blood Transfusion.
authors.forename: H
authors.initials: H
authors.lastname: Roelofs
authors.affiliation: Department of Immunohaematology and Blood Transfusion.
authors.forename: W E
authors.initials: WE
authors.lastname: Fibbe
authors.affiliation: Department of Clinical Pharmacy and Toxicology.
authors.forename: J
authors.initials: J
authors.lastname: Oostendorp
authors.affiliation: Department of Pathology and.
authors.forename: I
authors.initials: I
authors.lastname: Bajema
authors.affiliation: Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: M I M
authors.initials: MI
authors.lastname: Versteegh
authors.affiliation: From the Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Taube
authors.affiliation: From the Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: P S
authors.initials: PS
authors.lastname: Hiemstra
mesh_terms: D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000166:cytology; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply / Q000601:surgery; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011013:Pneumonectomy; D011446:Prospective Studies; D011656:Pulmonary Emphysema / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D012720:Severity of Illness Index; D017154:Stromal Cells / Q000637:transplantation*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1
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