Repeated intravenous doses of human umbilical cord-derived mesenchymal stromal cells for bronchopulmonary dysplasia: results of a phase 1 clinical trial with 2-year follow-up

Background: Currently, there is a lack of effective treatments or preventive strategies for bronchopulmonary dysplasia (BPD). Pre-clinical studies with mesenchymal stromal cells (MSCs) have yielded encouraging results. The safety of administering repeated intravenous doses of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs) has not yet been tested in extremely-low-gestational-age newborns (ELGANs). Aims: to test the safety and feasibility of administering three sequential intravenous doses of UC-MSCs every 7 days to ELGANs at risk of developing BPD. Methods: In this phase 1 clinical trial, we recruited ELGANs (birth weight <= 1250 g and <= 28 weeks in gestational age [GA]) who were on invasive mechanical ventilation (IMV) with FiO2 >= 0.3 at postnatal days 7-14. Three doses of 5 x 10 6 /kg of UC-MSCs were intravenously administered at weekly intervals. Adverse effects and prematurity-related morbidities were recorded. Results: From April 2019 to July 2020, 10 patients were recruited with a mean GA of 25.2 +/- 0.8 weeks and a mean birth weight of 659.8 +/- 153.8 g. All patients received three intravenous UC-MSC doses. The first dose was administered at a mean of 16.6 +/- 2.9 postnatal days. All patients were diagnosed with BPD. All patients were discharged from the hospital. No deaths or any serious adverse events related to the infusion of UCMSCs were observed during administration, hospital stays or at 2-year follow-up. Conclusions: The administration of repeated intravenous infusion of UC-MSCs in ELGANs at a high risk of developing BPD was feasible and safe in the short- and mid-term follow-up. (c) 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)