(P-BT-24) The randomized, placebo-controlled, double-blinded phase I trial of autologous cord blood mononuclear cell infusion for very preterm monozygotic twins

Background/Case Studies: Persistent perinatal inflammation plays a crucial role in the pathogenesis of preterm complications. Immunomodulation effect was an important mechanism underlying the beneficial results of stem cell therapies. Cord blood was regarded as a convenient source of stem cells. Our and others’ clinical studies had showed cord blood cells infusion are both safe and possibly effective in prevention and treatment for preterm complication in single birth. The hereditary material is the same between the monozygotic twins, which were considered as the ideal human subjects. However, previous studies excluded this special population, which was also faced with high risk of complications. Until now, there was no study on the feasibility and safety of cord blood cell therapy in very preterm monozygotic twins (VPMT). This randomized, placebo-controlled, double-blinded phase I clinical trial aimed to assess the feasibility, safety and initial effect of intravenous ACBMNC infusion in VPMT. In addition, we investigated the immunomodulatory effect.

Study

Design/Methods: Inborn VPMTs less than 32 gestational weeks received intravenous ACBMNC infusion (targeted at 1-10×107 cells/kg) or placebo (normal saline) within 24 hours after birth in a 1:1 ratio inside the twins.The primary objective of the study was determine whether ACBMNC intervention was feasible, safe and iimproved clinical symptoms. The secondary objectives were to assess the immunomodulatory effect via multi-omics approach.

Results/Findings: From November 28, 2021 to August 18, 2022, 8 pairs of VPMTs received ACBMNC ranging from 2.5-7.5×107 cells/kg or placebo within 24 hours after birth. Intravenously administration of ACBMNCs was feasible , well tolerated and led to a reduction trend in preterm associated complications, and was safe in long term. No serious adverse events were observed. We also noticed significant increase in Treg proportion, various decreased inflammatory cytokines level, favorable lung microbiota community. Furthermore, ACBMNC intervention induced transcriptional upregulation of processes in Treg differentiation in immune cells.

Conclusions: Our findings nominated ACBMNC intervention as a potent immunomodulatory therapy and protective intervention for alleviating preterm complications for very preterm infants, which warranted further investigation in larger trials.

Importance of research: Our findings nominated ACBMNC intervention as a potent immunomodulatory therapy and protective intervention for alleviating preterm complications for very preterm infants, which warranted further investigation in larger trials.