Modulation of cardiac macrophages by phosphatidylserine-presenting liposomes improves infarct repair
Tamar Harel-Adara, Tamar Ben Mordechaib, Yoram Amsalemb, Micha S. Feinbergb, Jonathan Leorb, and Smadar Cohena,1
+ Author Affiliations
aAvram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel; and
bNeufeld Cardiac Research Institute, Tel Aviv University, Sheba Medical Center, Tel-Hashomer, 52621, Israel
Edited* by Robert Langer, Massachusetts Institute of Technology, Cambridge, MA, and approved December 17, 2010 (received for review October 20, 2010)
Herein we investigated a new strategy for the modulation of cardiac macrophages to a reparative state, at a predetermined time after myocardial infarction (MI), in aim to promote resolution of inflammation and elicit infarct repair. The strategy employed intravenous injections of phosphatidylserine (PS)-presenting liposomes, mimicking the anti-inflammatory effects of apoptotic cells. Following PS-liposome uptake by macrophages in vitro and in vivo, the cells secreted high levels of anti-inflammatory cytokines [transforming growth factor β (TGFβ) and interleukin 10 (IL-10)] and upregulated the expression of the mannose receptor—CD206, concomitant with downregulation of proinflammatory markers, such as tumor necrosis factor α (TNFα) and the surface marker CD86. In a rat model of acute MI, targeting of PS-presenting liposomes to infarct macrophages after injection via the femoral vein was demonstrated by magnetic resonance imaging (MRI). The treatment promoted angiogenesis, the preservation of small scars, and prevented ventricular dilatation and remodeling. This strategy represents a unique and accessible approach for myocardial infarct repair.