Podoplanin regulates the migration of mesenchymal stromal cells and their interaction with platelets

Abstract

Mesenchymal stromal cells (MSC) up-regulate podoplanin at sites of infection, chronic inflammation, and cancer. We investigated the functional consequences of podoplanin expression on the migratory potential of MSC and their interactions with circulating platelets. Expression of podoplanin significantly enhanced the migration of MSC compared to MSC 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 MSC lacking podoplanin, indicating it was responsible for regulation of migration through podoplanin. When podoplanin-expressing MSC 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 were co-cultured on the apical surface. Confocal imaging shows podoplanin-expressing MSC extending processes into the EC layer, which could interact with circulating platelets. In both models, platelet aggregation induced by podoplanin-expressing MSC was inhibited by recombinant soluble CLEC-2. Thus, podoplanin may enhance the migratory capacity of tissue-resident MSC and enable novel interactions with cells expressing CLEC-2.