Prevention for moderate or severe BPD with intravenous infusion of autologous cord blood mononuclear cells in very preterm infants-a prospective non-randomized placebo-controlled trial and two-year follow up outcomes

• Published in: EClinicalMedicine 2023-03, Vol.57, p.101844-101844, Article 101844
• Main Authors: Zhuxiao, Ren, Fang, Xu, Wei, Wei, Shumei, Yang, Jianlan, Wang, Qiuping, Li, Jingjun, Pei, Chuan, Nie, Yongsheng, Li, Zhichun, Feng, Jie, Yang
• Format: Article
• Language: English
• Subjects: Autologous cord blood mononuclear cells; Bronchopulmonary dysplasia; Immunomodulation; Outcomes; Very preterm neonates
• ISSN: 2589-5370; 2589-5370
• DOI: 10.1016/j.eclinm.2023.101844

Bronchopulmonary dysplasia (BPD) is the primary severe complication of preterm birth. Severe BPD was associated with higher risks of mortality, more postnatal growth failure, long term respiratory and neurological developmental retardation. Inflammation plays a central role in alveolar simplification and dysregulated vascularization of BPD. There is no effective treatment to improve BPD severity in clinical practice. Our previous clinical study showed autologous cord blood mononuclear cells (ACBMNCs) infusion could reduce the respiratory support duration safely and potential improved BPD severity. Abundant preclinical studies have reported the immunomodulation effect as an important mechanism underlying the beneficial results of stem cell therapies in preventing and treating BPD. However, clinical studies assessing the immunomodulatory effect after stem cells therapy were rare. This study was to investigate the effect of ACBMNCs infusion soon after birth on prevention for severe BPD and long term outcomes in very preterm neonates. The immune cells and inflammatory biomarkers were detected to investigate the underlying immunomodulatory mechanisms. This single-center, prospective, investigator-initiated, non-randomized trial with blinded outcome assessment aimed to assess the effect of a single intravenous infusion of ACBMNCs in preventing severe BPD (moderate or severe BPD at 36 weeks of gestational age or discharge home) in surviving very preterm neonates less than 32 gestational weeks. Patients admitted to the Neonatal Intensive Care Unit (NICU) of Guangdong Women and Children Hospital from July 01, 2018 to January 1, 2020 were assigned to receiving a targeted dosage of 5 × 107 cells/kg ACBMNC or normal saline intravenously within 24 h after enrollment. Incidence of moderate or severe BPD in survivors were investigated as the primary short term outcome. Growth, respiratory and neurological development were assessed as long term outcomes at corrected age of 18–24 month-old. Immune cells and inflammatory biomarkers were detected for potential mechanism investigation. The trial was registered at ClinicalTrials.gov (NCT02999373). Six-two infants were enrolled, of which 29 were enrolled to intervention group, 33 to control group. Moderate or severe BPD in survivors significantly decreased in intervention group (adjusted p = 0.021). The number of patients needed to treat to gain one moderate or severe BPD-free survival was 5 (95% confidence interval: 3–20). Sur