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Tissue Engineering

Tissue Engineering - Poster Session E

Poster BB15 - Using Human Pluripotent Stem Cell-Derived Lung Organoids for Lung Regeneration

Saturday, October 26, 2024
10:00 AM - 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Stem cells have become increasingly popular as therapeutics to help regenerate tissue. Lung disease is a leading cause of death in America, and with stem cell therapies, we can provide new methods in treating damaged lungs. Lung organoids, derived from human pluripotent stem cells (hPSCs), are developed and equipped with pulmonary mesoderm and pulmonary endoderm, with the ability to develop into branching airway and early alveolar structures in the dish and recapitulate lung development when transplanted in vivo. Incorporating lung organoids into damaged lung could assist in regeneration of healthy lung cells, to potentially improve the function of diseased or damaged lungs. In this study, we delivered hPSC-lung organoids into damaged swine lung to promote lung regeneration. We hypothesized that the hPSC-derived lung organoids would engraft to the damaged lungs and better repair the injured lungs.

Materials and

Methods:  Two experimental groups were used: a prolonged maintenance swine lung and a gastric acid injured swine lung. hPSC-derived ZsGreen lung organoids were delivered either proximally to injured airways or distally to injured alveolar regions. After 8-33 hours in the healthy and injured lung, a small piece of each lung was collected for analyses. Samples were then sectioned with a cryostat (Leica) and underwent immunofluorescent staining with human EpCAM (Cell Signaling Technologies). Immunofluorescent microscopy (Leica) was performed to identify human lung organoids present in both healthy and injured swine lung.

Results, Conclusions, and Discussions: Our results confirm the presence of human lung organoids in the swine lung. Human EpCAM signaling is present in identical areas as ZsGreen signaling, verifying that the ZsGreen signaling that is seen coincides with our lung organoids (Fig. 1). This suggested that the lung organoids can survive and attach to injured lungs and can potentially be used as a source of cell therapy for regeneration of damaged lungs. While it has been confirmed that our cells are present in the swine lung, further detailed characterizations of these cells and their behaviors inside the lung will be needed. Future experiments will include staining for ciliated cells (FOXJ1, A-tubulin), basal cells (P63, Keratin 5), goblet cells (SCGB3A2, SCGB1A1, MUC5AC, MUC5B, MUC2), engraftment (Connexin 43, ZO1), and staining for distal regions (Caveolin 1, PDPN, SFTPC, SFTPB, ABCA3). Samples from different timepoints post hPSC-lung organoid delivery will be harvested and characterized (8 hours, 12 hours, and 33 hours). These preliminary findings provide a proof-of-concept of the potential of using hPSC-derived lung organoids for injured lung regeneration.

Acknowledgements (Optional):