Abstract 9899: Wnt11-Pretreated Bone Marrow Mesenchymal Stem Cells Induce Superior Cardiac Repair After a Reperfused Myocardial Infarction
Wnt11, a member of the evolutionarily conserved Wnt family of glycoproteins, plays important roles in cellular migration, proliferation, and differentiation during embryogenesis. However, the impact of Wnt11 signaling in cardiac repair after an acute myocardial infarction (MI) remains largely unknown. Based on the ability of Wnt11 to induce cardiomyogenic differentiation in adult cells, we hypothesized that pretreatment of bone marrow mesenchymal stem cells (MSCs) with Wnt11 would improve the outcomes of infarct repair. In vitro, Wnt11 pretreatment upregulated the expression of antiapoptotic and angiogenic molecules in MSCs. Wnt11 also increased the expression of Nkx2.5 (Figure), a marker of cardiac commitment. To test the efficacy of Wnt11 pretreatment on MSC-induced cardiac repair in vivo, MSCs were cultured in presence of Wnt11-secreting 293 cells (on an insert) for 5 days and transplanted intramyocardially after a reperfused MI. Age-matched male wild-type (C57BL/6J) mice underwent a 30-min coronary occlusion followed by reperfusion, and 48 h later received intramyocardial injection of vehicle, untreated MSCs (1 million in 30 microL), or Wnt11-pretreated MSCs (1 million in 30 microL). Echocardiography was performed 4 d prior to coronary occlusion/reperfusion (BSL1) and at 48 h (BSL2), 21 d, and 35 d after cell injection. After 35 d, compared with mice that received vehicle or untreated MSCs, mice injected with Wnt11-pretreated MSCs exhibited greater LV ejection fraction (Figure) and smaller LV end-diastolic volume, indicating that Wnt11 pretreatment transforms MSCs into superior vehicles of infarct repair. We conclude that intramyocardial transplantation of Wnt11-pretreated MSCs after a reperfused MI results in improved myocardial repair. These results underscore that pretreatment with Wnt11 may potentially enhance the outcomes of therapeutic infarct repair in humans.
- © 2011 by American Heart Association, Inc.