The Role of Bioactive Lipids in Stem Cell Mobilization and Homing: Novel Therapeutics for Myocardial Ischemia

Figure 2

Sequence of events in BMSPC mobilization from the BM towards ischemic myocardium during MI. Acute MI initiates an inflammatory response resulting in release of proteases (by granulocytes and osteoclasts) in the BM which proteolytically inactivate the SDF-1 CXCR4 interaction between BM osteoclasts and BMSPCS. The now mobilized BMSPCs follow an increasing SDF-1 and bioactive lipid (S1P and C1P) gradient to exit the BM niches into the PB. Acute inflammation also promotes the release of cathelicidins (LL-37) which facilitate clustering of CXCR4 into lipid rafts thereby increasing their sensitivity towards lower levels of circulating SDF-1. Together, the increased sensitivity towards SDF-1 and bioactive lipid gradients facilitate BMSPC homing towards ischemic myocardium.