title: Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical Trial.
abstract: Despite Food and Drug Administration approval of 2 new drugs for idiopathic pulmonary fibrosis (IPF), curative therapies remain elusive and mortality remains high. Preclinical and clinical data support the safety of human mesenchymal stem cells as a potential novel therapy for this fatal condition. The Allogeneic Human Cells (hMSC) in patients with Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER) trial was the first study designed to evaluate the safety of a single infusion of bone marrow-derived mesenchymal stem cells in patients with idiopathic pulmonary fibrosis.
  
  
  
  Nine patients with mild to moderate IPF were sequentially assigned to 1 of 3 cohorts and dosed with a single IV infusion of 20, 100, or 200 × 106human bone marrow-derived mesenchymal stem cells per infusion from young, unrelated, men. All baseline patient data were reviewed by a multidisciplinary study team to ensure accurate diagnosis. The primary end point was the incidence (at week 4 postinfusion) of treatment-emergent serious adverse events, defined as the composite of death, nonfatal pulmonary embolism, stroke, hospitalization for worsening dyspnea, and clinically significant laboratory test abnormalities. Safety was assessed until week 60 and additionally 28 days thereafter. Secondary efficacy end points were exploratory and measured disease progression.
  
  
  
  No treatment-emergent serious adverse events were reported. Two nontreatment-related deaths occurred because of progression of IPF (disease worsening and/or acute exacerbation). By 60 weeks postinfusion, there was a 3.0% mean decline in % predicted FVC and 5.4% mean decline in % predicted diffusing capacity of the lungs for carbon monoxide.
  
  
  
  Data from this trial support the safety of a single infusion of human mesenchymal stem cells in patients with mild-moderate IPF.
  
  
  
  ClinicalTrials.gov; No.: NCT02013700; URL: www.clinicaltrials.gov.
authors.affiliation: Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL; Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL; Department of Pediatrics, University of Miami Leonard M. Miller School of Medicine, Miami, FL. Electronic address: mglassbe@med.miami.edu.
authors.forename: Marilyn K
authors.initials: MK
authors.lastname: Glassberg
authors.affiliation: Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL.
authors.forename: Julia
authors.initials: J
authors.lastname: Minkiewicz
authors.affiliation: Department of Medicine, Florida International University Herbert Wertheim College of Medicine, Miami, FL.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Toonkel
authors.affiliation: Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL.
authors.forename: Emmanuelle S
authors.initials: ES
authors.lastname: Simonet
authors.affiliation: Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Rubio
authors.affiliation: Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL; University of Miami Interdisciplinary Stem Cell Institute, Miami, FL.
authors.forename: Darcy
authors.initials: D
authors.lastname: DiFede
authors.affiliation: Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL.
authors.forename: Shirin
authors.initials: S
authors.lastname: Shafazand
authors.affiliation: Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL; University of Miami Interdisciplinary Stem Cell Institute, Miami, FL.
authors.forename: Aisha
authors.initials: A
authors.lastname: Khan
authors.affiliation: Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL; University of Miami Interdisciplinary Stem Cell Institute, Miami, FL.
authors.forename: Marietsy V
authors.initials: MV
authors.lastname: Pujol
authors.affiliation: Department of Cardiology, University of Louisville, Louisville, KY.
authors.forename: Vincent F
authors.initials: VF
authors.lastname: LaRussa
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Lancaster
authors.affiliation: Bristol-Myers Squibb, Lawrenceville, NJ.
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Rosen
authors.affiliation: Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL.
authors.forename: Joel
authors.initials: J
authors.lastname: Fishman
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, VT.
authors.forename: Yolanda N
authors.initials: YN
authors.lastname: Mageto
authors.affiliation: The EMMES Corporation, Rockville, MD.
authors.forename: Adam
authors.initials: A
authors.lastname: Mendizabal
authors.affiliation: Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL; University of Miami Interdisciplinary Stem Cell Institute, Miami, FL.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D002248:Carbon Monoxide; D018450:Disease Progression; D004417:Dyspnea; D005260:Female; D006760:Hospitalization; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008875:Middle Aged; D009026:Mortality; D011653:Pulmonary Diffusing Capacity; D011655:Pulmonary Embolism / Q000453:epidemiology; D020521:Stroke / Q000453:epidemiology; D014109:Total Lung Capacity; D014184:Transplantation, Homologous; D014797:Vital Capacity; D000070857:Walk Test
chemical_list: D002248:Carbon Monoxide
keywords: bone marrow; idiopathic pulmonary fibrosis; mesenchymal stem cells; safety trial