Mesenchymal Stem Cell Therapy in Severe Neonatal Bronchopulmonary Dysplasia: a Longitudinal Translational Study in Preterm Twins

Background: Severe bronchopulmonary dysplasia (BPD) remains a major cause of long-term respiratory morbidity in extremely preterm infants, with limited disease-modifying treatment options. Mesenchymal stromal cell (MSC)–based therapies have emerged as a promising investigational approach; however, clinical evidence remains limited, particularly regarding longitudinal outcome assessment. Methods: This retrospective, longitudinal twin case study evaluated two extremely preterm twin infants with severe BPD who received intravenous umbilical cord–derived MSC therapy under a regulated clinical attempt approved by the Turkish Ministry of Health. Baseline was defined as the time of first MSC administration (postnatal day 30), with follow-up at approximately 1, 3, and 6 months. Longitudinal outcomes included arterial blood gas parameters, clinical respiratory severity scores, ventilatory support requirements, radiologic lung injury scores, and lung compliance assessments. Outcomes were evaluated descriptively without inferential statistical analysis. Results: Both patients demonstrated progressive improvement in gas exchange, clinical respiratory distress, ventilatory support requirements, radiologic lung injury, and lung compliance during follow-up. Despite comparable baseline disease severity, recovery trajectories differed between the twins, with one patient showing more rapid and complete improvement across multiple domains. Improvements were observed during the follow-up period after UC-MSC administration and were sustained across the available longitudinal assessments. Conclusion: This study describes the longitudinal respiratory outcomes of two extremely preterm twins who had severe BPD and were treated with IV UC-MSC therapy under a regulated clinical study framework. During follow-up, physiological, clinical, and radiologic improvements were observed with divergent recovery trajectories despite shared genetic and early environmental backgrounds. However, this study included only two patients and lacked a control group. These observations are hypothesis-generating and should be interpreted in the context of ongoing standard-of-care treatment, natural postnatal lung maturation, and the variable clinical course of severe BPD. Larger prospective controlled studies are needed to define safety and efficacy, optimal timing and dosing strategy, patient selection, and long-term respiratory and neurodevelopmental outcomes. Lay Summary: Bronchopulmonary dysplasia (BPD) is a serious lung disease that affects premature infants causing long-term breathing problems. Current treatments mainly support breathing but do not directly repair damaged lung tissue. In this study, we examined clinical outcomes of two premature twin infants with severe BPD receiving mesenchymal stem cell (MSC) therapy as part of a regulated clinical treatment. Both infants showed improvements in breathing, oxygen needs, lung imaging and function over 6 months of follow-up; however, the degree of recovery differed between them. Our findings suggest that MSC therapies may support lung repair in severe BPD and warrant further clinical investigation.