Adipose Stem Cells Derived Exosomes Alleviate Bronchopulmonary Dysplasia and Regulate Autophagy in Neonatal Rats


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Abstract

Background::Mesenchymal stem cell-derived exosomes (MSC-Exos) therapies have shown prospects in preclinical models of pathologies relevant to neonatal medicine, such as bronchopulmonary dysplasia (BPD). Adipose-derived stem cells (ADSCs) have been recognized as one of the most promising stem cell sources. Autophagy plays a key role in regulating intracellular conditions, maintaining cell growth and development, and participating in the pathogenesis of BPD.

Objectives::To investigate the potential therapeutic role of ADSC-Exos on BPD and to illustrate the role of autophagy in this process.

Method::ADSC-Exos was isolated from media conditioned of ADSCs by ultracentrifugation and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting (WB). Newborn rats were exposed to hyperoxia (90% O2) from postnatal day 0 (P0) to P7, and returned to room air until P14 to mimic BPD. ADSC-Exos was treated by intratracheal or intravenous administration on P4. Treated animals and appropriate controls were harvested on P7 and P14 for assessment of pulmonary parameters.

Results::Hyperoxia-exposed rats were presented with pronounced alveolar simplification with decreased radial alveolar count (RAC) and increased mean linear intercept (MLI), impaired vascular development with low vascular endothelial growth factor (VEGF) and CD31 expression, and stimulated inflammation with increased expression of TNF-α, IL-1β, and IL-6, and decreased expression of IL-10. Meanwhile, the rats with hyperoxia exposure blocked autophagic flux with lower levels of Beclin1, LC3B, LC3BII/I ratio and higher levels of p62. ADSC-Exos administration protected the neonatal lung tissues from the hyperoxia-induced arrest of alveolar and vascular development, reduced inflammation, and facilitated autophagy. Intratracheal administration was more efficacious than intravenous administration

Conclusion::The intratracheal administration of ADSC-Exos significantly improved alveolarization and pulmonary vascularization arrest in hyperoxia-induced BPD, which was associated with facilitating autophagy in part.

About the authors

Yuanyuan Sun

, Wenzhou Medical University

Email: info@benthamscience.net

Cuie Chen

Department of Pediatrics, Yiwu Maternity and Children Hospital,

Email: info@benthamscience.net

Yuanyuan Liu

Department of Pediatrics, the First Affiliated Hospital of Wenzhou Medical University,

Email: info@benthamscience.net

Anqun Sheng

Department of Pediatrics,, the First Affiliated Hospital of Wenzhou Medical University,

Email: info@benthamscience.net

Shi Wang

Department of Anesthesiology, Women’s Hospital School of Medicine Zhejiang University,

Email: info@benthamscience.net

Xixi Zhang

Department of Pediatrics, Yuhuan People’s Hospital

Email: info@benthamscience.net

Dan Wang

Department of Pediatrics, the First Affiliated Hospital of Wenzhou Medical University,

Email: info@benthamscience.net

Qiu Wang

Department of Pediatrics, the First Affiliated Hospital of Wenzhou Medical University,

Email: info@benthamscience.net

Chaosheng Lu

Department of Pediatrics, the First Affiliated Hospital of Wenzhou Medical University

Email: info@benthamscience.net

Zhenlang Lin

, Wenzhou Medical University

Author for correspondence.
Email: info@benthamscience.net

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