Late Breaking Abstract - Aminopeptidase N/CD13 distinguishes two populations of colony-forming mesenchymal stromal cells in human lung tissue

Abstract

Background: It is hypothesized that different populations of mesenchymal cells, including mesenchymal stromal cells (MSC), have specific involvement in chronic lung disease, however some populations have a suggested regenerative function. The limited description of this mesenchymal cell heterogeneity and lack of specific markers makes it difficult to understand their endogenous function, further impeding development of therapeutic approaches targeting aberrant mesenchymal cell activity. Aim: To explore the heterogeneity of MSCs in lung tissue and to identify functionally different subpopulations. Methods: Mesenchymal cells were isolated from human donor lungs and healthy regions from lung tumor resections, and characterized using fluorescence-activated cell sorting (FACS) in combination with in vitro assays for colony formation and VEGF production (ELISA). Results: We identified Aminopeptidase N/CD13 as a marker that distinguished two distinct cell populations (CD13neg/low and CD13high) in a MSC enriched population (CD45neg/CD31neg/CD105pos/CD90pos). By FACS we observed that colony-forming MSCs were highly enriched in the CD45neg/CD31neg/EpCAMneg/CD105pos fraction and that they derived from both CD90pos/CD13neg/low and CD90pos/CD13high populations. Interestingly, preliminary data showed that cells from the CD90pos/CD13neg/low population had an increased production of VEGF and lower proliferation compared to cells from the CD90pos/CD13high population. Conclusion: Our data suggests that CD90pos/CD13neg/low and CD90pos/CD13high lung-derived MSC are functionally different. This highlights the need to understand the complexity within the mesenchymal cell populations in lung.