# An Interventional Study on the Late Treatment of Severe Bronchopulmonary Dysplasia in Preterm Infants Using Mesenchymal Stromal Cells

## TL;DR

This study explores using mesenchymal stromal cells to treat severe lung disease in preterm infants, finding that multiple treatment cycles improve outcomes and reduce complications.

## Contribution

The study introduces a late-term MSC therapy approach for severe BPD, demonstrating effectiveness through multiple treatment cycles and combined delivery routes.

## Key findings

- Infants receiving three to four MSC cycles were successfully weaned off ventilators and discharged without oxygen support.
- MSC therapy showed secondary benefits like reduced intraventricular hemorrhage and fewer sepsis episodes.
- Combined intratracheal and intravenous MSC delivery may provide systemic benefits beyond lung function.

## Abstract

Bronchopulmonary dysplasia (BPD) remains a significant challenge in the management of preterm infants. Although conventional treatment approaches have helped reduce the morbidity associated with BPD, the prevalence of the condition has not decreased, highlighting an urgent need for new therapies. Mesenchymal stromal cell (MSC) therapy has emerged as a potentially promising intervention, showing a favorable safety profile in Phase II clinical trials. However, research on the use of MSCs as a late‐term therapeutic strategy for established BPD is still in its early stages, indicating a need for further studies to evaluate their effectiveness and optimal application.

To investigate the results of seven extremely preterm infants who underwent an MSC therapy for severe established BPD.

A cohort of seven infants diagnosed with severe BPD (sBPD) received MSC therapy to assist in their transition to spontaneous breathing. For the first six infants, MSC therapy was discontinued after extubation; however, the final infant continued to receive MSC therapy as he remained on nasal continuous positive airway pressure (nCPAP).

Each treatment cycle involved administering 1 million MSCs per kilogram via intratracheal injection, along with an additional 0.5 million MSCs delivered through intravenous infusion. Treatment was initiated between postnatal days 32 and 84. The first three infants each underwent two treatment cycles, the fourth infant received three cycles, and the last three infants were scheduled for 4 weekly cycles. A retrospective analysis was conducted to evaluate the outcomes of the therapy.

All infants were successfully extubated to nCPAP following MSC treatment. However, two infants who underwent two cycles of MSC therapy could not be weaned off respiratory support. In contrast, all infants who received three to four cycles were successfully weaned off the ventilators and discharged home without the need for supplemental oxygen. Additionally, secondary benefits were observed, including improvements in intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP), a decrease in the number of packed red blood cell transfusions, and fewer episodes of sepsis.

Our findings indicate that administering up to four treatment cycles may be more effective for the long‐term management of sBPD. Additionally, using MSCs through both intratracheal and intravenous routes could offer benefits beyond just the lungs, highlighting an area for further research.