MAST CELLS IMPROVE CARDIAC FUNCTION TRANSIENTLY AFTER AN MI AND MODULATE DIFFERENTIATION/PROLIFERATION STAGE OF MESENCHYMAL STEM CELLS THROUGH PDGF

Mast cells (MCs) were originally considered as just multifunctional effectors of allergy. However, recent studies have indicated their involvement in other physiological and pathological processes. The existence of MCs in the myocardium has been recognized. However, the exact function of these cells in cardiac pathology remains undefined. Aside from their remarkable potential to produce and release of a wide array of bio-active mediators, a dramatic increase in MC numbers following myocardial infarction suggests their importance in the cardiac wound healing process. I hypothesized that MCs can perform reparative functions when implanted to the site of cardiac injury. MCs were prepared from bone marrow, studied, and implanted into the myocardium of a mouse model of myocardial infarction. The results indicated MC implantation transiently improved cardiac function. Further investigation demonstrated that the beneficial impacts of MC implantation were associated with greater angiogenesis and myofibroblastic responses, which countered the augmented inflammatory response. Additionally, studies of MC-mesenchymal stem cell (MSC) interactions demonstrated that MSCs oscillate between proliferative and more-differentiated states and that MCs promote proliferation and suppress myogenic differentiation in MSCs through platelet derived growth factor and its downstream mediators miR-143/145. The pro-proliferative actions of MCs enlarge the MSC pool prior to differentiation, thereby ultimately facilitating elevated MSC-origin myofibroblast numbers. These new insights unveil beneficial MC involvement in cardiac repair and regeneration beyond their role in post-MI early inflammation.Ph.D