Regenerative capacity of alveolar type 2 cells is proportionally reduced following disease progression in idiopathic pulmonary fibrosis-derived organoid cultures.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that leads to respiratory failure and death due to irreversible scarring of the distal lung. While historically considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now recognized to play a central role in IPF pathophysiology. PURPOSE: This study aimed to investigate the regenerative capacity of AT2 cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. METHOD: Lung tissues from 3 pneumothorax patients and 6 IPF patients (early and advanced stages) were obtained by VATS and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-EpCAM+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immuno-staining was used to confirm the presence of AT2 cells. RESULTS: FACS sorting yielded approximately 1% AT2 cells of the total cells in early IPF tissue, and the number decreased as the disease progressed, compared with 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller in size and fewer in number compared to those from pneumothorax patients. The colony-forming efficiency decreased as the disease progressed. In immuno-staining results, the IPF organoids showed lower expression of SFTPC compared to the pneumothorax group and contained KRT5+ cells. CONCLUSION: This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, and IPF AT2 cells inherently exhibit functional abnormalities and altered differentiation plasticity.

Hepatic Infarction Caused by Portal Vein Thrombophlebitis Misdiagnosed as Infiltrative Hepatic Malignancy with Neoplastic Thrombus.

Portal vein thrombosis (PVT) is a form of venous thrombosis that usually presents in chronic form without any sequalae in patients with hepatocellular carcinoma (HCC) or liver cirrhosis. Accurate differential diagnosis of bland PVT from neoplastic PVT is an important step for planning treatment options, but the acute form can be challenging. Here we present a case of acute hepatic infarction caused by acute bland PVT combined with pylephlebitis, which was misdiagnosed as infiltrative hepatic malignancy with neoplastic PVT owing to the perplexing imaging results and elevated tumor markers.