title: A phase 1b study of placenta-derived mesenchymal stromal cells in patients with idiopathic pulmonary fibrosis.
abstract: OBJECTIVE
  Idiopathic pulmonary fibrosis (IPF) is a degenerative disease characterized by fibrosis following failed epithelial repair. Mesenchymal stromal cells (MSC), a key component of the stem cell niche in bone marrow and possibly other organs including lung, have been shown to enhance epithelial repair and are effective in preclinical models of inflammation-induced pulmonary fibrosis, but may be profibrotic in some circumstances.
  
  
  METHODS
  In this single centre, non-randomized, dose escalation phase 1b trial, patients with moderately severe IPF (diffusing capacity for carbon monoxide (DLCO ) ≥ 25% and forced vital capacity (FVC) ≥ 50%) received either 1 × 10(6) (n = 4) or 2 × 10(6) (n = 4) unrelated-donor, placenta-derived MSC/kg via a peripheral vein and were followed for 6 months with lung function (FVC and DLCO ), 6-min walk distance (6MWD) and computed tomography (CT) chest.
  
  
  RESULTS
  Eight patients (4 female, aged 63.5 (57-75) years) with median (interquartile range) FVC 60 (52.5-74.5)% and DLCO 34.5 (29.5-40)% predicted were treated. Both dose schedules were well tolerated with only minor and transient acute adverse effects. MSC infusion was associated with a transient (1% (0-2%)) fall in SaO2 after 15 min, but no changes in haemodynamics. At 6 months FVC, DLCO , 6MWD and CT fibrosis score were unchanged compared with baseline. There was no evidence of worsening fibrosis.
  
  
  CONCLUSIONS
  Intravenous MSC administration is feasible and has a good short-term safety profile in patients with moderately severe IPF.
authors.affiliation: Queensland Lung Transplant Service, The Prince Charles Hospital; School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Chambers
authors.forename: Debra
authors.initials: D
authors.lastname: Enever
authors.forename: Nina
authors.initials: N
authors.lastname: Ilic
authors.forename: Lisa
authors.initials: L
authors.lastname: Sparks
authors.forename: Kylie
authors.initials: K
authors.lastname: Whitelaw
authors.forename: John
authors.initials: J
authors.lastname: Ayres
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Yerkovich
authors.forename: Dalia
authors.initials: D
authors.lastname: Khalil
authors.forename: Kerry M
authors.initials: KM
authors.lastname: Atkinson
authors.forename: Peter M A
authors.initials: PM
authors.lastname: Hopkins
mesh_terms: D000368:Aged; D017079:Exercise Tolerance; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008875:Middle Aged; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D011653:Pulmonary Diffusing Capacity; D016896:Treatment Outcome; D014797:Vital Capacity
keywords: cell therapy; idiopathic pulmonary fibrosis; infusion; mesenchymal stromal cells; short-term safety