A phase 1b study of placenta-derived mesenchymal stromal cells in patients with idiopathic pulmonary fibrosis

Background and objectiveIdiopathic 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. MethodsIn 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 1x10(6) (n=4) or 2x10(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. ResultsEight 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 SaO(2) after 15min, 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. ConclusionsIntravenous MSC administration is feasible and has a good short-term safety profile in patients with moderately severe IPF. Preclinical studies support the efficacy of intravenous MSC therapy in bleomycin-induced pulmonary inflammation/fibrosis; however, the potential to worsen established fibrosis remains a concern. In this first-in-man study, we show that intravenous MSC therapy is feasible and has a satisfactory short-term safety profile in human idiopathic pulmonary fibrosis.