Isolation of alveolar epithelial type II progenitor cells from adult human lungs

Abstract

Resident stem/progenitor cells in the lung are important for tissue homeostasis and repair. However, a progenitor population for alveolar type II (ATII) cells in adult human lungs has not been identified. The aim of this study is to isolate progenitor cells from adult human lungs with the ability to differentiate into ATII cells. We isolated colony-forming cells that had the capability for self-renewal and the potential to generate ATII cells in vitro. These undifferentiated progenitor cells expressed surface markers of mesenchymal stem cells (MSCs) and surfactant proteins associated with ATII cells, such as CD90 and pro-surfactant protein-C (pro-SP-C), respectively. Microarray analyses indicated that transcripts associated with lung development were enriched in the pro-SP-C+/CD90+ cells compared with bone marrow-MSCs. Furthermore, pathological evaluation indicated that pro-SP-C and CD90 double-positive cells were present within alveolar walls in normal lungs, and significantly increased in ATII cell hyperplasias contributing to alveolar epithelial repair in damaged lungs. Our findings demonstrated that adult human lungs contain a progenitor population for ATII cells. This study is a first step toward better understanding of stem cell biology in adult human lung alveoli.

Future prospects for tissue engineered lung transplantation

“…Alveolar progenitor cells (AEPCs) isolated from human lungs, c-kit-positive cells, and E-Cadherin and leucinerich repeat-containing G-protein-coupled receptor 6 double positive (E-Cad/Lgr6 + ) cells might have the potential for differentiation into lung specific lineages. 58,59 Fujino and colleagues demonstrated that AEPCs have an epithelial phenotype with an MSC character. According to microarray analysis, AEPCs share many genes with AETII cells and mesenchymal stem cells, which suggests an overlapping phenotype with both the alveolar epithelium and the mesenchyme in these cells.…”

“…According to microarray analysis, AEPCs share many genes with AETII cells and mesenchymal stem cells, which suggests an overlapping phenotype with both the alveolar epithelium and the mesenchyme in these cells. 58 Kajstura and colleagues isolated c-kit-positive cells from adult human lungs and when the cell population was injected into injured lungs of C57BL/6 mice, the cells differentiated not only into epithelial cells, but also into mesenchymal and endothelial cells without rejection. 59 …”

Pulmonary administration of phosphoinositide 3-kinase inhibitor is a curative treatment for chronic obstructive pulmonary disease by alveolar regeneration

“…The gaseous alveolar surface is lined by alveolar type I cells (AT-I) and alveolar type II cells (AT-II) [6]. Recent studies have characterized resident alveolar stem cells in human [7]. However, potent regenerative compounds have not been identified for human alveolar stem cells.…”

Molecular basis of lung tissue regeneration

“…85,86 Some adenocarcinomas have shown a phenotype similar to that of alveolar epithelial progenitor cells. 75 These data suggest that some lung cancer cells have stem cell characteristics and thus may be cancer stem cells. Further research is needed in this area.…”

“…Then, we isolated human alveolar progenitor cells (AEPCs) from the StemSurvive-preserved human lungs. 75 AEPCs represent an epithelial phenotype with mesenchymal stem cell character. According to microarray analyses, AEPCs share many genes with mesenchymal stem cells (MSCs) and ATII cells (Fig.…”