Endobronchial autologous bone marrow-mesenchymal stromal cells in idiopathic pulmonary fibrosis: a phase I trial

Arantza Campo, José María González-Ruiz, Enrique Andreu, Ana B Alcaide, María M Ocón, Juan De-Torres, Jesús Pueyo, Rosa Cordovilla, Eva Villaron, Fermín Sanchez-Guijo, Miguel Barrueco, Jorge Nuñez-Córdoba, Felipe Prósper, Javier J Zulueta, Arantza Campo, José María González-Ruiz, Enrique Andreu, Ana B Alcaide, María M Ocón, Juan De-Torres, Jesús Pueyo, Rosa Cordovilla, Eva Villaron, Fermín Sanchez-Guijo, Miguel Barrueco, Jorge Nuñez-Córdoba, Felipe Prósper, Javier J Zulueta

Abstract

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

Objectives: To 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 multicentre clinical trial (ClinicalTrials.gov NCT01919827) with a single endobronchial administration of autologous adult BM-MSCs in patients diagnosed with mild-to-moderate IPF. In a first escalating-dose phase, three patients were included sequentially in three dose cohorts (10×106, 50×106 and 100×106 cells). In a second phase, nine patients received the highest tolerated dose. Follow-up with pulmonary function testing, 6-min walk test and St George's Respiratory Questionnaire was done at 1, 2, 3, 6 and 12 months, and with computed tomography at 3, 6 and 12 months.

Results: 21 bone marrow samples were obtained from 17 patients. Three patients were excluded from treatment due to chromosome aberrations detected in MSCs after culture, and one patient died before treatment. Finally, 13 patients received the BM-MSC infusion. No treatment-related severe adverse events were observed during follow-up. Compared to baseline, the mean forced vital capacity showed an initial decline of 8.1% at 3 months. The number of patients without functional progression was six (46%) at 3 months and three (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.

Conflict of interest statement

Conflict of interest: A. Campo has nothing to disclose. Conflict of interest: J.M. González-Ruiz has nothing to disclose. Conflict of interest: E. Andreu has nothing to disclose. Conflict of interest: A.B. Alcaide has nothing to disclose. Conflict of interest: M.M. Ocón has nothing to disclose. Conflict of interest: J. De-Torres has nothing to disclose. Conflict of interest: J. Pueyo has nothing to disclose. Conflict of interest: R. Cordovilla has nothing to disclose. Conflict of interest: E. Villaron has nothing to disclose. Conflict of interest: F. Sanchez-Guijo reports lecturing and consulting honoraria, and research support from Novartis; lecturing and consulting honoraria from BMS, Pfizer, Incyte and Gilead; and lecturing honoraria from Roche and Amgen, all outside the submitted work. Conflict of interest: M. Barrueco has nothing to disclose. Conflict of interest: J. Nuñez-Córdoba has nothing to disclose. Conflict of interest: F. Prosper has nothing to disclose. Conflict of interest: J.J. Zulueta has nothing to disclose.

Copyright ©The authors 2021.

Figures

FIGURE 1
FIGURE 1
Study flow diagram for treatment. Patients identified by 01-XX. BM: bone marrow.
FIGURE 2
FIGURE 2
Individual changes in a) forced vital capacity (FVC) and b) diffusing capacity of the lung for carbon monoxide (DLCO) during follow-up.

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