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Human induced pluripotent stem cells ameliorate hyperoxia-induced lung injury in a mouse model
Adam Mitchell1, Heather Wanczyk1, Todd Jensen1
1University of Connecticut Health Center 263 Farmington Ave, Farmington, CT, USA.
Insights
Human induced pluripotent stem cells (iPSCs) show promise in repairing lung damage caused by hyperoxia in neonatal mice. This research offers potential new therapies for preventing bronchopulmonary dysplasia.
Area of Science:
- Regenerative Medicine
- Neonatal Physiology
- Pulmonary Biology
Background:
- Hyperoxia-induced lung injury is a significant complication in premature neonates requiring oxygen support.
- Bronchopulmonary dysplasia (BPD) is a chronic lung disease that can result from this injury, with limited effective treatments.
- Human induced pluripotent stem cells (iPSCs) offer a potential therapeutic avenue for tissue repair.
Purpose of the Study:
- To investigate the efficacy of human induced pluripotent stem cells (iPSCs) and differentiated iPSCs (diPSCs) in repairing hyperoxia-induced lung damage in a neonatal mouse model.
- To evaluate the impact of iPSC and diPSC treatments on inflammatory gene expression and lung histomorphometry.
- To assess the therapeutic potential of exosomes derived from iPSCs and diPSCs as a cell-free alternative.
Main Methods:
- Neonatal mice were exposed to 75% oxygen for 6 or 14 days to induce lung injury.
- Intra-oral administration of iPSCs, diPSCs, or their derived exosomes was performed post-exposure.
- Histomorphometric analysis (mean linear intercept) and gene expression analysis of inflammatory markers (Tgfβ1, Nfkb1, Il-6) were conducted.
- Control groups included hyperoxia, normoxia, and vehicle treatment.
Main Results:
- iPSC treatment significantly improved lung structure, normalizing the mean linear intercept to levels comparable to normoxic controls.
- iPSC treatment led to the normalization of inflammatory gene expression (Tgfβ1, Nfkb1, Il-6) within 14 days post-treatment in mice exposed to 6 days of hyperoxia.
- Differentiated iPSCs (diPSCs) and exosomes were less effective in reversing hyperoxia-induced lung damage compared to iPSCs.
Conclusions:
- Human induced pluripotent stem cells (iPSCs) demonstrate significant potential in repairing hyperoxia-induced lung injury in a neonatal mouse model.
- iPSC therapy may modulate the inflammatory response, offering a promising strategy for preventing bronchopulmonary dysplasia.
- Further research into iPSC-based therapies could lead to novel treatments for acute lung injury in neonates.
Abstract:
Hyperoxia-induced lung injury occurs in neonates on oxygen support due to premature birth, often leading to the development of bronchopulmonary dysplasia. Current treatment options have limited effect. The aim of this study was to determine if human induced pluripotent stem cells (iPSCs) and those differentiated to an alveolar-like phenotype (diPSCs) could repair hyperoxia-induced lung damage in a mouse model. Neonatal C57BL6/J mice were separated into two groups and exposed to 75% oxygen over 6 or 14 days. Cell treatments were instilled intra-orally following removal. Controls included hyperoxia, normoxia, and a vehicle. 7 and 14 days post treatment, lungs were extracted and histomorphometric analysis performed. Gene expression of markers mediating inflammation (Tgfβ1, Nfkb1, and Il-6) were investigated. In addition, exosomes from each cell type were isolated and administered as a cell free alternative. There was a significant difference between the mean linear intercept (MLI) in hyperoxic vs. normoxic lungs prior to treatment. No difference existed between the MLI in iPSC-treated lungs vs. normoxic lungs after 6 and 14 days of hyperoxia. For mice exposed to 6 days of hyperoxia, gene expression in iPSC-treated lungs returned to normal 14 days later. At the same time points, diPSCs were not as effective. Exosomes were also not as effective in reversing hyperoxic lung damage as their cellular counterparts. This study highlights the potential benefit of using iPSCs to repair damaged lung tissue through possible modulation of the inflammatory response, leading to novel therapies for acute hyperoxia-induced lung injury and the prevention of bronchopulmonary dysplasia.
