Assessing the impact of gestational age of donors on the efficacy of amniotic epithelial cell-derived extracellular vesicles in experimental bronchopulmonary dysplasia

Dandan Zhu; Mirja Krause; Tamara Yawno; Gina D Kusuma; Renate Schwab; Mehri Barabadi; Amina S Maleken; Siow T Chan; Rod Hunt; David Greening; Euan M Wallace; Rebecca Lim

doi:10.1186/s13287-022-02874-4

Assessing the impact of gestational age of donors on the efficacy of amniotic epithelial cell-derived extracellular vesicles in experimental bronchopulmonary dysplasia

Stem Cell Res Ther. 2022 May 12;13(1):196. doi: 10.1186/s13287-022-02874-4.

Authors

Dandan Zhu^{1

2}, Mirja Krause^{1

2}, Tamara Yawno^{3

4

5}, Gina D Kusuma^{1

2}, Renate Schwab^{1

2}, Mehri Barabadi¹, Amina S Maleken^{1

2}, Siow T Chan^{1

2}, Rod Hunt⁶, David Greening^{7

8

9

10}, Euan M Wallace^{1

2}, Rebecca Lim^{1

2}

Affiliations

¹ The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia.
² Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, 3168, Australia.
³ The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia. tamara.yawno@monash.edu.
⁴ Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, 3168, Australia. tamara.yawno@monash.edu.
⁵ Department of Paediatrics, Monash University, Clayton, VIC, 3168, Australia. tamara.yawno@monash.edu.
⁶ Department of Paediatrics, Monash University, Clayton, VIC, 3168, Australia.
⁷ Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
⁸ Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.
⁹ Central Clinical School, Monash University, Clayton, VIC, Australia.
¹⁰ Baker Department of Cardiometabolic Health, University of Melbourne, Parkville, VIC, Australia.

Abstract

Background and rationale: Extracellular vesicles (EVs) are a potential cell-free regenerative medicine. Human amniotic epithelial cells (hAECs) are a viable source of cell therapy for diseases like bronchopulmonary dysplasia (BPD). However, little is known about the impact of gestational age of the donor on the quality of hAEC-derived EVs.

Aims: To determine the impact of gestational age on hAEC-derived EVs in experimental BPD.

Results: Term hAEC-derived EVs displayed a significantly higher density of surface epitopes (CD142 and CD133) and induced greater macrophage phagocytosis compared to preterm hAEC-EVs. However, T cell proliferation was more significantly suppressed by preterm hAEC-EVs. Using a model of experimental BPD, we observed that term but not preterm hAEC-EVs improved tissue-to-airspace ratio and septal crest density. While both term and preterm hAEC-EVs reduced the levels of inflammatory cytokines on postnatal day 7, the improvement in lung injury was associated with increased type II alveolar cells which was only observed in term hAEC-EV treatment group. Furthermore, only neonatal term hAEC-EVs reduced airway hyper-responsiveness, mitigated pulmonary hypertension and protected against right ventricular hypertrophy at 6 weeks of age.

Conclusion: Term hAEC-EVs, but not preterm hAEC-EVs, have therapeutic efficacy in a mouse model of BPD-like lung injury. Therefore, the impact of donor criteria should be considered when applying perinatal cells-derived EV therapy for clinical use.

Keywords: Bronchopulmonary dysplasia; Extracellular vesicles; Human amniotic epithelial cells; Prematurity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bronchopulmonary Dysplasia* / metabolism
Bronchopulmonary Dysplasia* / therapy
Epithelial Cells
Extracellular Vesicles* / metabolism
Female
Gestational Age
Humans
Infant, Newborn
Lung Injury* / therapy
Mice
Pregnancy