Podoplanin regulates the migration of mesenchymal stromal cells and their interaction with platelets
Lewis S C Ward1, Lozan Sheriff2, Jennifer L Marshall1
1Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK.
Abstract:
Mesenchymal stromal cells (MSCs) upregulate podoplanin at sites of infection, chronic inflammation and cancer. Here, we investigated the functional consequences of podoplanin expression on the migratory potential of MSCs and their interactions with circulating platelets. Expression of podoplanin significantly enhanced the migration of MSCs compared to MSCs lacking podoplanin. Rac-1 inhibition altered the membrane localisation of podoplanin and in turn significantly reduced MSC migration. Blocking Rac-1 activity had no effect on the migration of MSCs lacking podoplanin, indicating that it was responsible for regulation of migration through podoplanin. When podoplanin-expressing MSCs were seeded on the basal surface of a porous filter, they were able to capture platelets perfused over the uncoated apical surface and induce platelet aggregation. Similar microthrombi were observed when endothelial cells (ECs) were co-cultured on the apical surface. Confocal imaging shows podoplanin-expressing MSCs extending processes into the EC layer, and these processes could interact with circulating platelets. In both models, platelet aggregation induced by podoplanin-expressing MSCs was inhibited by treatment with recombinant soluble C-type lectin-like receptor 2 (CLEC-2; encoded by the gene Clec1b). Thus, podoplanin may enhance the migratory capacity of tissue-resident MSCs and enable novel interactions with cells expressing CLEC-2.
Insights
Podoplanin enhances mesenchymal stromal cell (MSC) migration and platelet aggregation, potentially via Rac-1 and C-type lectin-like receptor 2 (CLEC-2) interactions. This suggests a role for podoplanin in MSC trafficking and immune responses.
Area of Science:
- Cell Biology
- Immunology
- Biochemistry
Background:
- Mesenchymal stromal cells (MSCs) are crucial for tissue repair and immune modulation.
- Podoplanin expression is observed in MSCs at sites of infection, inflammation, and cancer.
- The functional role of podoplanin in MSC behavior remains largely unexplored.
Purpose of the Study:
- To investigate the impact of podoplanin expression on MSC migration.
- To elucidate the role of Rac-1 in podoplanin-mediated MSC migration.
- To examine the interaction between podoplanin-expressing MSCs and platelets.
Main Methods:
- Assessing MSC migration with and without podoplanin expression.
- Utilizing Rac-1 inhibition to study its role in migration.
- Co-culturing MSCs with endothelial cells and perfusing platelets.
- Employing confocal imaging to visualize cell interactions.
- Testing the effect of soluble C-type lectin-like receptor 2 (CLEC-2) on platelet aggregation.
Main Results:
- Podoplanin expression significantly enhanced MSC migration.
- Rac-1 inhibition reduced podoplanin-dependent MSC migration.
- Podoplanin-expressing MSCs captured platelets and induced aggregation, forming microthrombi.
- MSC processes extended into endothelial cell layers, interacting with platelets.
- Platelet aggregation was inhibited by soluble CLEC-2.
Conclusions:
- Podoplanin expression enhances MSC migratory capacity.
- Rac-1 is essential for podoplanin-mediated MSC migration.
- Podoplanin facilitates novel interactions between MSCs and platelets, potentially via CLEC-2.
- These findings suggest podoplanin plays a role in MSC trafficking and immune cell interactions at inflammatory sites.
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