Assessing the impact of gestational age of donors on the efficacy of amniotic epithelial cell-derived extracellular vesicles in experimental bronchopulmonary dysplasia
journal contributionposted on 2022-06-21, 06:52 authored by Dandan Zhu, Mirja Krause, Tamara Yawno, Gina D Kusuma, Renate Schwab, Mehri Barabadi, Amina S Maleken, Siow T Chan, Hunt Rod, David GreeningDavid Greening, Euan M Wallace, Rebecca Lim
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.
This work was supported by NHMRC Project grants #1057741 and #1139489. RL is supported by a National Health and Medical Research Council Career Development Fellowship (Industry). We note further support by Helen Amelia Hains Fellowship (to DG) and by the Victorian State Government Operational Infrastructure funding to the Baker Institute.
JournalStem Cell Research and Therapy
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ANGIOGENESISBronchopulmonary dysplasiaCD133(+) CELLSCell & Tissue EngineeringCell BiologyEXOSOMESExtracellular vesiclesHuman amniotic epithelial cellsINTERNATIONAL SOCIETYLife Sciences & BiomedicineMedicine, Research & ExperimentalMESENCHYMAL STEM-CELLSMONOCYTE CHEMOATTRACTANT PROTEIN-1NEONATAL LUNG INJURYPOSITION STATEMENTPrematurityResearch & Experimental MedicineScience & TechnologyTNF-ALPHATRANSPLANTATIONAnimalsBronchopulmonary DysplasiaEpithelial CellsExtracellular VesiclesFemaleGestational AgeHumansInfant, NewbornLung InjuryMicePregnancyClinical Sciences not elsewhere classifiedPaediatrics and Reproductive Medicine not elsewhere classified