title: A placebo-controlled, randomized trial of mesenchymal stem cells in COPD.
abstract: BACKGROUND
  COPD is a devastating disease affecting millions worldwide. As disease pathogenesis includes both chronic pulmonary and systemic inflammation, antiinflammatory effects of systemically administered mesenchymal stem cells (MSCs) may decrease inflammation, resulting in improved lung function and quality of life. The goal of this study was to assess safety and to perform an initial evaluation of the potential efficacy of systemic MSC administration to patients with moderate to severe COPD.
  
  
  METHODS
  Sixty-two patients at six sites were randomized to double-blinded IV infusions of either allogeneic MSCs (Prochymal; Osiris Therapeutics Inc) or vehicle control. Patients received four monthly infusions (100 × 10⁶ cells/infusion) and were subsequently followed for 2 years after the first infusion. End points included comprehensive safety evaluation, pulmonary function testing (PFT), and quality-of-life indicators including questionnaires, 6MWT, and assessments of systemic inflammation.
  
  
  RESULTS
  All study patients completed the full infusion protocol, and 74% completed the 2-year follow-up. There were no infusional toxicities and no deaths or serious adverse events deemed related to MSC administration. There were no significant differences in the overall number of adverse events, frequency of COPD exacerbations, or worsening of disease in patients treated with MSCs. There were no significant differences in PFTs or quality-of-life indicators; however, an early, significant decrease in levels of circulating C-reactive protein (CRP) was observed in patients treated with MSCs who had elevated CRP levels at study entry.
  
  
  CONCLUSIONS
  Systemic MSC administration appears to be safe in patients with moderate to severe COPD and provides a basis for subsequent cell therapy investigations.
  
  
  BACKGROUND
  ClinicalTrials.gov; No.: NCT00683722; URL: www.clinicaltrials.gov.
authors.affiliation: Vermont Lung Center, University of Vermont College of Medicine, Burlington, VT. Electronic address: dweiss@uvm.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weiss
authors.affiliation: Los Angeles Biomedical Research Institute, Harbor-University of California, Los Angeles (UCLA) Medical Center, Torrance, CA.
authors.forename: Richard
authors.initials: R
authors.lastname: Casaburi
authors.affiliation: Osiris Therapeutics Inc, Columbia, MD.
authors.forename: Robin
authors.initials: R
authors.lastname: Flannery
authors.affiliation: Osiris Therapeutics Inc, Columbia, MD.
authors.forename: Michelle
authors.initials: M
authors.lastname: LeRoux-Williams
authors.affiliation: David Geffen School of Medicine, UCLA, Los Angeles, CA.
authors.forename: Donald P
authors.initials: DP
authors.lastname: Tashkin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008875:Middle Aged; D010919:Placebos; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D012129:Respiratory Function Tests; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D010919:Placebos