Stem Cells for Bronchopulmonary Dysplasia in Preterm Infants: A Randomized Controlled Phase II Trial

Abstract

We previously demonstrated the safety and feasibility of mesenchymal stem cell (MSC) transplantation for bronchopulmonary dysplasia (BPD) in preterm infants in a phase I clinical trial. We thus investigated the therapeutic efficacy of MSCs for BPD in premature infants. A phase II double-blind, randomized, placebo-controlled clinical trial was conducted on preterm infants at 23 to 28 gestational weeks (GW) receiving mechanical ventilator support with respiratory deterioration between postnatal days 5 and 14. Infants were stratified by 23 to 24 GW and 25 to 28 GW and randomly allocated (1:1) to receive stem cells (1 × 10 7 cells/kg, n = 33) or placebo (n = 33). Although the inflammatory cytokines in the tracheal aspirate fluid were significantly reduced with MSCs, the primary outcome of death or severe/moderate BPD in the control group (18/33, 55%) was not significantly improved with MSC transplantation (17/33, 52%). In the subgroup analysis, the secondary outcome of severe BPD was significantly improved from 53% (8/15) to 19% (3/16) with MSC transplantation in the 23 to 24 GW group but not in the 25 to 28 GW subgroup. In summary, although MSC transplantation might be safe and feasible, this small study was underpowered to detect its therapeutic efficacy in preterm infants at 23 to 28 GW. Accordingly, we are now conducting an additional larger and controlled phase II clinical trial focusing on infants at 23 to 24 GW (NCT03392467). ClinicalTrials.gov identifier: NCT01828957.

Diagnosis and management of bronchopulmonary dysplasia

“…198 Findings from a phase II RCT investigating the effect of intratracheal administration of MSCs to preterm infants of 23-28 weeks' gestational age showed a reduction in the incidence of severe BPD in a subgroup of infants born at 23-24 weeks' gestational age (19% treatment group [3/16] versus 53% placebo group [8/15]). 199 A larger multicenter phase II trial focusing on the use of intratracheally delivered MSCs in infants of 23-25 weeks' gestational age is under way (NCT03392467). A clinical trial evaluating the safety of intravenously administered bone marrow MSC derived extracellular vesicles in preterm infants of 23-26 weeks' gestational age is also in progress (NCT03857841).…”

“…Mesenchymal stem cell (MSC) based therapies have shown great potential for the management of a range of different neonatal conditions including BPD 198. Findings from a phase II RCT investigating the effect of intratracheal administration of MSCs to preterm infants of 23-28 weeks’ gestational age showed a reduction in the incidence of severe BPD in a subgroup of infants born at 23-24 weeks’ gestational age (19% treatment group [3/16] versus 53% placebo group [8/15]) 199. A larger multicenter phase II trial focusing on the use of intratracheally delivered MSCs in infants of 23-25 weeks’ gestational age is under way (NCT03392467).…”

An Update on the Prevention and Management of Bronchopulmonary Dysplasia

“…142 Results from a recently concluded Phase II trial demonstrated safety and feasibility of MSCs in preterm infants between 23 and 28 weeks gestation, although it was underpowered to detect therapeutic efficacy towards preventing BPD, and larger clinical trials are underway. 143 MSC-derived extracellular vesicles have pro-regenerative and immune modulating effects and have been shown to improve lung morphology, pulmonary function and suppress inflammation in animal models. 144 While these findings are promising, their clinical implications are yet to be established.…”

Mesenchymal Stromal Cells for the Treatment of Interstitial Lung Disease in Children: A Look from Pediatric and Pediatric Surgeon Viewpoints

“…In order to further evaluate the efficacy and safety of stem cell therapy for BPD, a long-term clinical trial is underway for children up to the age of 5 years (NCT02023788) for patients who completed the earlier part of the previous phase I clinical trial (NCT01632475). Ahn et al [ 162 ] performed a larger, double-blind, randomized, phase II clinical trial aimed at evaluating the therapeutic efficacy of transplantation with hUCB-MSCs (NCT01828957). The study enrolled 60 extremely premature infants, aged between 23 and 28 gestational weeks, with BPD.…”