Introduction: Idiopathic pulmonary fibrosis (IPF) is a lethal degenerative disease characterised 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 pulmonary fibrosis, but may be pro-fibrotic in some circumstances. The aim of this study was to confirm the feasibility and safety, particularly with respect to adverse acute haemodynamic effects and pro-fibrosis, of intravenous MSC therapy in humans with IPF.
Methods: In this single centre, non-randomised, dose escalation phase 1b trial (NCT01385644), patients with moderately severe IPF (DLCO>25% and FVC>50%) received either 1 (n=4) or 2*106 (n=4) placenta-derived MSC/kg via a peripheral vein from an unrelated donor and were followed for 6 months with lung function, 6 minute walk distance (6WMD) and CT chest.
Results: 8 patients (4 female, aged 63.5 (57-75) years) with median (IQR) FVC 60(52.5-74.5)%, DLCO 34.5 (29.5-40)%, 6MWD 460(375.5-540)m and CT fibrosis score 14.8(12.9-17.05)% were treated. Both dose schedules were well tolerated with only minor and transient acute adverse effects. MSC infusion was associated with a transient (1%) fall in SaO2 after 15 minutes, but no changes in haemodynamics. There was a transient improvement in 6WMD at 3 months. At 6 months FVC, DLCO, 6MWD and CT fibrosis score were all unchanged compared to baseline (p>0.05 for all measures). There was no evidence of worsening fibrosis.
Conclusion: This world first study has confirmed the feasibility and safety of intravenous MSC therapy in patients with moderately severe IPF.