Background Disrupted immunity and microbiota dysbiosis underlie the pathophysiology of preterm complications. This study investigated the effect of autologous cord blood (ACB)-mononuclear cells (MNCs) infusion, rich in stem cells, on immune microecology in very preterm infants (VPIs). Methods One twin from each enrolled very preterm monozygotic pair was randomized to receive an ACB-MNCs infusion or normal saline. Immune cells, inflammatory cytokine profiles, and gut/lung microbiota, were compared. Short- and long-term clinical outcomes were evaluated. Results ACB-MNCs intervention induced transcriptional up-regulation of regulatory T cells (Treg) differentiation-facilitating genes and increased circulating Tregs. In blood, post-ACB-MNCs infusion, pro-inflammatory factors decreased, while the IL-10 level was higher than in the control group. In the ACB-MNCs group, lung microbial diversity increased significantly after intervention. Post-intervention, lung IL-10 and TGF-β increased in the ACB-MNCs group and were higher than the control group, while pro-inflammatory factors IL-4, IL-17 A, and IL-6 levels decreased in the ACB-MNCs group. In the ACB-MNCs group, gut microbial diversity improved and was more metabolically active after intervention. After intervention, mainly upregulated differentially expressed genes in peripheral blood immune cells were positively correlated with favored microbes colonizing the lung. Lung IL-10 correlated positively with blood Treg frequency, while lung IL-10 and TGF-β correlated negatively with blood IL-17A. The gut microbial diversity was negatively associated with blood IL-17A. Compared with control group, the total number of distinct preterm complications per patient in the ACB-MNCs group were fewer and long-term linear growth was better. Conclusion ACB-MNCs intervention promoted immunity homeostasis via modulation of Treg and lung/gut microbiota. Trial registration This study was registered at Clinicaltrials.gov (NCT05087498). Date of registration: 10/09/2021; date of enrollment of the first participant to the trial:11/28/2021URL of trial registry record: <a href="https://clinicaltrials.gov/study/NCT05087498?term=NCT05087498%26rank=1">https://clinicaltrials.gov/study/NCT05087498?term=NCT05087498&rank=1</a>. Graphical Abstract

Autologous Cord Blood Mononuclear Cells Modulate Immunity and the Microbiota in Very Preterm Twins: A Randomized Trial

期刊论文
发表日期：

2026年4月28日

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Zhuxiao Ren,
Chuan Nie,
Fang Xu,
Weiwei Gao,
Shumei Yang,
Jiangxue Han,
Wei Wei,
Sophie Y. Yang,
Qi Zhang,
Jie Yang

摘要

Background

Disrupted immunity and microbiota dysbiosis underlie the pathophysiology of preterm complications. This study investigated the effect of autologous cord blood (ACB)-mononuclear cells (MNCs) infusion, rich in stem cells, on immune microecology in very preterm infants (VPIs).

Methods

One twin from each enrolled very preterm monozygotic pair was randomized to receive an ACB-MNCs infusion or normal saline. Immune cells, inflammatory cytokine profiles, and gut/lung microbiota, were compared. Short- and long-term clinical outcomes were evaluated.

Results

ACB-MNCs intervention induced transcriptional up-regulation of regulatory T cells (Treg) differentiation-facilitating genes and increased circulating Tregs. In blood, post-ACB-MNCs infusion, pro-inflammatory factors decreased, while the IL-10 level was higher than in the control group. In the ACB-MNCs group, lung microbial diversity increased significantly after intervention. Post-intervention, lung IL-10 and TGF-β increased in the ACB-MNCs group and were higher than the control group, while pro-inflammatory factors IL-4, IL-17 A, and IL-6 levels decreased in the ACB-MNCs group. In the ACB-MNCs group, gut microbial diversity improved and was more metabolically active after intervention.

After intervention, mainly upregulated differentially expressed genes in peripheral blood immune cells were positively correlated with favored microbes colonizing the lung. Lung IL-10 correlated positively with blood Treg frequency, while lung IL-10 and TGF-β correlated negatively with blood IL-17A. The gut microbial diversity was negatively associated with blood IL-17A. Compared with control group, the total number of distinct preterm complications per patient in the ACB-MNCs group were fewer and long-term linear growth was better.

Conclusion

ACB-MNCs intervention promoted immunity homeostasis via modulation of Treg and lung/gut microbiota.

Trial registration

This study was registered at Clinicaltrials.gov (NCT05087498). Date of registration: 10/09/2021; date of enrollment of the first participant to the trial:11/28/2021URL of trial registry record: https://clinicaltrials.gov/study/NCT05087498?term=NCT05087498&rank=1.

Graphical Abstract