2. Academic Validation
  3. HucMSCs-derived Exosomes Promote Lung Development in Premature Birth via Wnt5a/ROCK1 Axis

HucMSCs-derived Exosomes Promote Lung Development in Premature Birth via Wnt5a/ROCK1 Axis

  • Stem Cell Rev Rep. 2024 Nov 20. doi: 10.1007/s12015-024-10824-1.
Xin Li 1 2 3 4 5 6,  Lidong Huang 7,  Min Mao 1 2 3 4 5 6,  Hong Xu 1 2 3 4 5 6,  Caijun Liu 1 2 3 4 5 6,  Yang Liu 8 9 10 11 12 13,  Hanmin Liu 14 15 16 17 18 19
Affiliations

Affiliations

  • 1 Department of Pediatric Pulmonology and Immunology, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China.
  • 2 Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, People's Republic of China.
  • 3 NHC Key Laboratory of Chronobiology, Sichuan University, Chengdu, People's Republic of China.
  • 4 The Joint Laboratory for Lung Development and Related Diseases of West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China.
  • 5 School of Life Sciences of Fudan University, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China.
  • 6 Sichuan Birth Defects Clinical Research Center, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China.
  • 7 University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
  • 8 Department of Pediatric Pulmonology and Immunology, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China. cyggly@126.com.
  • 9 Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, People's Republic of China. cyggly@126.com.
  • 10 NHC Key Laboratory of Chronobiology, Sichuan University, Chengdu, People's Republic of China. cyggly@126.com.
  • 11 The Joint Laboratory for Lung Development and Related Diseases of West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China. cyggly@126.com.
  • 12 School of Life Sciences of Fudan University, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China. cyggly@126.com.
  • 13 Sichuan Birth Defects Clinical Research Center, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China. cyggly@126.com.
  • 14 Department of Pediatric Pulmonology and Immunology, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China. liuhm@scu.edu.cn.
  • 15 Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, People's Republic of China. liuhm@scu.edu.cn.
  • 16 NHC Key Laboratory of Chronobiology, Sichuan University, Chengdu, People's Republic of China. liuhm@scu.edu.cn.
  • 17 The Joint Laboratory for Lung Development and Related Diseases of West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China. liuhm@scu.edu.cn.
  • 18 School of Life Sciences of Fudan University, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China. liuhm@scu.edu.cn.
  • 19 Sichuan Birth Defects Clinical Research Center, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China. liuhm@scu.edu.cn.
PMID: 39565502 DOI: 10.1007/s12015-024-10824-1
Abstract

Bronchopulmonary dysplasia (BPD) frequently affects extremely preterm and low birth weight infants, with current treatments lacking specificity. Enhancing extra-uterine preterm alveoli development and repairing damage are crucial for BPD management. Here we show that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-Exos) can enhance fetal lung development in mice by delivering specific contents. Briefly, hucMSCs-Exos were extracted using ultracentrifugation and identified by transmission electron microscopy (TEM), flow cytometry, Western blot (WB), and nanoparticle tracking analysis (NTA). These exosomes were then administered to pregnant mice via tail vein injection. Embryonic lung tissues were collected at E13.5 and E18.5 via cesarean section and analyzed using hematoxylin-eosin (HE) staining, immunofluorescence, and TEM. Proteomic analysis was conducted to identify protein components in the exosomes, and WB was used to assess protein expression changes. hucMSCs-Exos from full-term infants were more effective in promoting cell proliferation than those from preterm infants. In vivo, full-term hucMSCs-Exos significantly enhanced alveolarization in fetal lung tissues. Proteomic analysis revealed higher Wnt5a expression in full-term hucMSCs-Exos, and further experiments confirmed a direct interaction between Wnt5a and ROCK1. WB also showed increased expression of the Autophagy marker LC3B in the lung tissues of mice treated with full-term exosomes. In conclusion, term hucMSCs-Exos may directly regulate the phosphorylation of ROCK1 in mouse lung tissue through naturally enriched Wnt5a, thus promoting Autophagy of AT2 cells and lamellar body development, and ultimately enhance the alveolarization and reducing the incidence of BPD in premature infants.

Keywords

Bronchopulmonary Dysplasia; Exosome; Lamellar body; Lung Development; Wnt5a.

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