Cell & Stem Cell Research

Mesenchymal stem cells (MSC) are tissue resident stromal cells with immunomodulatory properties which are increasing used therapeutically via injection into the blood. Within the blood and tissue, their adhesive and migration properties, along with their interactions with other blood cells may influence their fate. Human bone marrow (BM) or umbilical cord (UC) MSC adhered from flow to matrix proteins. However, they displayed distinct interactions with platelets when perfused in whole blood, with only UCMSC inducing platelet aggregation and causing a marked drop in platelet count when infused systematically into mice. UCMSC, but not BMMSC, expressed a mucin-like protein called podoplanin, which is known to bind to CLEC-2 expressed on platelets. Expression of podoplanin varied in UCMSC donors; most were positive, but some donors lacked expression (podoplanin negative). Only podoplanin-positive UCMSC were able to aggregate platelets in vitro and in vivo, and this could be blocked by competitive inhibition with recombinant CLEC-2. Human UCMSC caused reduction of platelet count when mixed with mouse blood, but the response was lost with blood taken from mice deficient in CLEC-2. Separately we observed that podoplanin expression enhanced UCMSC migration in vitro in a Rac-1 dependent manner. Thus, the origins of MSC and their expression of podoplanin may have impact on their behavior in blood and tissue. During therapy, MSC interactions with platelets could be thrombotic, but might also promote targeting of MSC to damaged tissue, where they could exert their reparative and immunomodulatory effects.