Marilyn K. Glassberg, Julia Minkiewicz, Rebecca L. Toonkel, Emmanuelle S. Simonet, Gustavo A. Rubio, Darcy DiFede, Shirin Shafazand, Aisha Khan, Marietsy V. Pujol, Vincent F. LaRussa, Lisa H. Lancaster, Glenn D. Rosen, Joel Fishman, Yolanda N. Mageto, Adam Mendizabal, Joshua M. Hare

Despite recent FDA approval of two new drugs for idiopathic pulmonary fibrosis (IPF), curative therapies remain elusive and mortality remains high. Pre-clinical and clinical data support the safety of human mesenchymal stem cells as a potential novel therapy for this fatal condition. The 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 one of three cohorts and dosed with a single intravenous infusion of 20, 100, or 200 x 10(6) human bone marrow-derived mesenchymal stem cells per infusion from young, unrelated, male donors. All baseline patient data were reviewed by a multidisciplinary study team to ensure accurate diagnosis. The primary endpoint was the incidence (at week four post infusion) of treatment emergent serious adverse events, defined as the composite of: death, non-fatal 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 endpoints were exploratory and measured disease progression. No treatment-emergent serious adverse events were reported. Two non-treatment related deaths occurred due to progression of IPF (disease worsening and/or acute exacerbation). By 60 weeks post-infusion, there was a 3.0% mean decline in % predicted FVC and 5.4% mean decline in % predicted DLCO. Data from this trial support the safety of a single infusion of hMSC in patients with mild-moderate IPF.