Endobronchial autologous bone marrow-mesenchymal stromal cells in idiopathic pulmonary fibrosis (phase I)

Rationale Idiopathic pulmonary fibrosis (IPF) has a dismal prognosis. Mesenchymal stromal cells have shown benefit in other inflammatory diseases.

Objectives Evaluate the safety and feasibility of endobronchial administration of bone marrow autologous MSCs (BM-MSC) in patients with mild-to-moderate IPF.

Methods A phase-I multicenter clinical Trial (ClinicalTrials.gov:NCT01919827) with a single endobronchial administration of autologous adult BM-MSC in patients diagnosed with mild-to-moderate IPF. In a first escalating-dose phase, 3 patients will be included sequentially in 3 dose cohorts (10×10^6, 50×10^6, and 100×10^6 cells). In a second phase, 9 patients will receive the highest tolerated dose. Follow-up with PFT, 6MWT, and SGRQ were done at 1, 2, 3, 6, and 12 months, and with a computed tomography at 3, 6, and 12 months.

Findings Twenty-one bone marrow samples were obtained from 17 patients. Three patients were excluded for treatment due to chromosome aberrations detected in MSCs after culture, and one patient died before treatment. Finally, 13 patients received the BM-MSCs infusion. No treatment related severe adverse events were observed during follow-up. Compared to baseline, the mean FVC showed an initial decline of 8.1% at three months. The number of patients without functional progression was 6 (46%) at 3 months and 3 (23%) at 12 months.

Conclusions The endobronchial infusion of BM-MSCs did not cause immediate serious adverse events in IPF patients, but a relevant proportion of patients suffered clinical and/or functional progression. Genomic instability of BM-MSCs during culture found in three patients may be troublesome for the use of autologous MSCs in IPF patients.