Human induced pluripotent stem cell-derived lung progenitor and alveolar epithelial cells attenuate hyperoxia-induced...

Area of Science:

• Regenerative Medicine
• Stem Cell Biology
• Neonatal Lung Development

Background:

• Bronchopulmonary dysplasia (BPD) is a chronic lung disease common in premature infants, characterized by impaired lung growth and persistent pulmonary issues.
• Alveolar epithelial type 2 cells (AEC2s), including lung progenitor cells (LPCs), are crucial for normal lung development and repair.
• AEC2 depletion is implicated in the persistent lung injury observed in BPD.

Purpose of the Study:

• To investigate the potential of induced pluripotent stem cell (iPSC)-derived AECs as a therapeutic strategy for experimental oxygen-induced BPD.
• To assess the safety and efficacy of hiPSC-derived AEC2s and hiPSC-derived LPCs in preventing lung damage in a neonatal mouse model of BPD.

Main Methods:

• Various cell types, including primary mouse AECs, murine pluripotent stem cells, human umbilical cord mesenchymal stromal cells (hUCMSCs), undifferentiated human (h)iPSCs, hiPSC-derived LPCs, and hiPSC-derived AECs, were intratracheally delivered to hyperoxia-exposed newborn mice.
• Cells were pre-labeled with a red fluorescent dye for in vivo tracking to monitor engraftment and distribution.
• A highly efficient differentiation protocol was employed to generate a homogenous population of hiPSC-derived AEC2s for therapeutic evaluation.

Main Results:

• Airway delivery of primary mouse AECs and undifferentiated murine pluripotent cells protected neonatal mice from hyperoxia-induced lung function and alveolar growth impairment.
• Undifferentiated hiPSCs, similar to hUCMSC therapy, preserved lung function and alveolar growth in hyperoxia-exposed mice, but long-term assessment revealed teratoma formation.
• Intratracheal administration of hiPSC-derived AEC2s and hiPSC-derived LPCs significantly improved lung function and structure, demonstrating long-term engraftment without evidence of tumor formation.

Conclusions:

• hiPSC-derived AEC2 therapy demonstrates both efficacy and safety in a preclinical model of BPD.
• This cell-based therapy warrants further investigation as a potential treatment for BPD and other lung diseases involving AEC injury.
• The development of a clinically relevant cell therapy using hiPSC-derived AECs offers a promising avenue for managing neonatal lung diseases.