Cord blood stem cell‑derived Angptl7 ameliorates the severity of bronchopulmonary dysplasia via anti‑inflammatory and proangiogenic effects

Ren,Zhuxiao; Yang,Liling; Wang,Jianlan; Han,Jiangxue; Lin,Shouheng; Yao,Yao; Du,Chen; Yang,Jie

doi:10.3892/mmr.2023.13131

Cord blood stem cell‑derived Angptl7 ameliorates the severity of bronchopulmonary dysplasia via anti‑inflammatory and proangiogenic effects

Authors:
- Zhuxiao Ren
- Liling Yang
- Jianlan Wang
- Jiangxue Han
- Shouheng Lin
- Yao Yao
- Chen Du
- Jie Yang
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Affiliations: Department of Neonatology, Guangdong Women and Children Hospital, Guangzhou, Guangdong 511442, P.R. China, Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 511400, P.R. China, Department of Neonatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 511422, P.R. China
Published online on: November 20, 2023 https://doi.org/10.3892/mmr.2023.13131
Article Number: 8
Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Perinatal exposure of the neonatal lung to inflammation leads to decreased lung angiogenesis and the development of bronchopulmonary dysplasia (BPD). Notably, autologous cord blood mononuclear cells (ACBMNCs) can substantially prevent severe BPD and decrease the inflammatory response in surviving very preterm neonates. Angiopoietin‑like protein 7 (Angptl7) is one of the main paracrine cytokines in cord blood stem cells, and is capable of stimulating human hematopoietic stem and progenitor cell expansion. The present study compared Angptl7 levels between the ACBMNCs infusion and control groups (cohort 1). Subsequently, the association between cord blood Angptl7 levels and BPD incidence in a cohort of very preterm neonates was assessed (cohort 2). The hypothesis was further verified in a lipopolysaccharide (LPS)‑induced lung injury mouse model. The mRNA expression levels and protein concentrations of inflammatory cytokines in the lung tissue and mouse serum were measured using reverse transcription‑quantitative PCR and ELISA, respectively. The number and diameter of lung vessels and macrophage infiltration were assessed using immunofluorescence staining. Compared with in the control group, Angptl7 levels were significantly higher in the ACBMNCs infusion group in cohort 1. In cohort 2, the cord blood Angptl7 levels were significantly lower in infants who later developed BPD. Multiple linear regression analysis showed that higher Angptl7 level was an independent protective factor for BPD. The concentrations of interleukin‑6 and monocyte chemoattractant protein‑1 were negatively correlated with cord blood Angptl7 level; whereas, vascular endothelial growth factor‑A levels were positively correlated with Angptl7 levels. In the LPS‑induced lung injury mouse model, the LPS group presented with a significant loss of pulmonary vessels and smaller vessel diameters, which were ameliorated in the Angptl7 treatment group. Furthermore, LPS‑induced lung inflammation and macrophage infiltration were alleviated by Angptl7 treatment (P<0.05). In conclusion, the anti‑inflammatory and proangiogenic effects of Angptl7 derived from cord blood stem cells may ameliorate BPD severity. The trial for cohort 1 was registered at ClinicalTrials.gov (trial registration no. NCT02999373; date registered, December 21, 2016).

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