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Effects of Mesenchymal Stem Cell Coculture on Human Lung Small Airway Epithelial Cells
Eva Schmelzer1, Vitale Miceli2, Cinzia Maria Chinnici3,4
1Department of Surgery, University of Pittsburgh, Pennsylvania, USA.
Abstract:
Mesenchymal stem cells (MSCs) and their secreted extracellular vesicles have been used effectively in different lung disease animal models and clinical trials. Their specific beneficial effects, the potential differences between MSCs derived from different organs, and interactions between MSC products and target cells still need to be studied further. Therefore, we investigated the effects of secreted products of human MSCs derived from the bone marrow and adipose tissue on human lung small airway epithelial (AE) cells in vitro. AE cells were cocultured with MSCs in inserts that allowed the free exchange of medium but did not allow direct cell-to-cell contact. We examined the effects on AE cell viability, proliferation, cell numbers, expression of AE cell-specific genes, and CD54 (intercellular adhesion molecule 1 (ICAM1)) surface positivity, as well as the secretion/uptake of growth factors relevant for AE cell. We found that coculture increased the viability of AE cells. The majority of AE cells expressed CD54 on their surface, but the percentage of cells being positive for CD54 did not increase in coculture. However, ICAM1 gene expression was increased in coculture. Also, we observed increased gene expression of mucin (MUC1), a lung-enriched cell surface glycoprotein. These observed effects were the same between bone marrow and adipose tissue MSCs. However, MSCs derived from adipose tissue reduced angiopoietin concentrations in coculture, whereas those from the bone marrow did not. Conclusively, MSCs influenced AE cells positively by increasing their viability and affecting gene expression, with some effects being specific for the tissue origin of MSCs.
Insights
Mesenchymal stem cells (MSCs) positively impact lung airway epithelial (AE) cells by enhancing viability and altering gene expression. These beneficial effects were consistent between bone marrow and adipose tissue-derived MSCs in vitro.
Area of Science:
- Regenerative Medicine
- Cell Biology
- Pulmonology
Background:
- Mesenchymal stem cells (MSCs) and their secreted extracellular vesicles show therapeutic promise in lung diseases.
- Further research is needed to understand MSC product interactions with target lung cells and differences between MSCs from various origins.
Purpose of the Study:
- To investigate the effects of human bone marrow-derived MSCs (BM-MSCs) and adipose tissue-derived MSCs (AT-MSCs) secreted products on human lung small airway epithelial (AE) cells in vitro.
- To compare the impact of BM-MSCs and AT-MSCs on AE cell viability, proliferation, gene expression, and growth factor profiles.
Main Methods:
- Co-culturing human AE cells with BM-MSCs or AT-MSCs using inserts that permit medium exchange but prevent direct cell contact.
- Assessing AE cell viability, proliferation, cell numbers, specific gene expression (ICAM1, MUC1), CD54 surface positivity, and growth factor concentrations.
Main Results:
- Co-culture with MSCs significantly increased AE cell viability.
- MSC co-culture elevated ICAM1 and MUC1 gene expression in AE cells.
- While both BM-MSCs and AT-MSCs showed similar effects on AE cell viability and gene expression, AT-MSCs uniquely reduced angiopoietin levels.
Conclusions:
- MSCs positively influence lung AE cells, enhancing viability and modulating gene expression, indicating potential therapeutic benefits.
- The tissue origin of MSCs (bone marrow vs. adipose tissue) can lead to specific differences in their secreted product profiles and effects on target cells.
