Jornal de pesquisa e terapia com células-tronco

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High-density Lipoproteins Induce the Migration Capacity of Mesenchymal Stromal Cells

Frank Spillmann, Kapka Kapka, Katrin Warstat, Stojan Perisic, Jochen Ringe, Carsten Tschöpe and Sophie Van Linthout

Background: Based on the regenerative capacity of HDL and their ability to induce migration of endothelial cells, we aimed to investigate whether HDL can influence the migration of mesenchymal stromal cells (MSC) and to analyze the underlying mechanisms. Methods and results: MSC express the SR-BI receptor as shown by flow cytometry. Supplementation of HDL or their main apolipoprotein (apo), apo A-I, induces the phosphorylation state of Akt and NO production in MSC. This is associated with an increase in lamellipodia formation as demonstrated via phallotoxin staining and further leads to an induction in migration capacity as indicated by a 1.4-fold (p<0.05) and 1.4-fold (p<0.05) higher presence of MSC in the lower chamber of a modified Boyden chamber supplemented with HDL or apo A-I, respectively, compared to basal medium. In addition, the migration capacity of MSC in a wound healing assay 24 h after scratching was 1.7- fold (p<0.05) and 1.2-fold (p<0.05) higher in HDL and apo A-Isupplemented hydroxyurea treated MSC compared to basal hydroxyurea-treated MSC. In both assays, the HDL or apo A-I stimulated migration of MSC was reduced in the presence of the phosphatidylinositol-3-kinase (PI3K) inhibitor Ly294002. Conclusion: HDL induces the migration of MSC in a PI3K-dependent manner.