Abstract 17476: Transplantation of an Antigenically-Defined Subpopulation of Bone Marrow Mesenchymal Stem Cells Results in Superior Cardiac Repair After a Reperfused Myocardial Infarction

Although bone marrow mesenchymal stem cells (MSCs) have been used quite extensively for cardiac repair, the outcomes have been highly variable. We investigated whether antigenically-defined subpopulations of MSCs would promote superior repair after myocardial infarction (MI). Unfractionated MSCs were obtained from the adherent fraction of bone marrow cells from C57BL/6 mice using expansion culture, and subpopulations were obtained using two-step FACS isolation. Our in vitro studies identified a Sca-1+/CD45-/c-kit-/Thy1+/CD105- MSC population (CD105- MSCs) that exhibited greater mRNA expression of angiogenic molecules (VEGF, HGF), SDF-1, and reduced expression of deleterious molecules, including TNF-a (Figure). The CD105- MSCs also exhibited greater propensity toward cardiac differentiation. The efficacy of these cells for cardiac repair in vivo was tested in a mouse model of reperfused MI. Wild-type (C57BL/6) mice underwent a 30-min coronary occlusion followed by reperfusion, and 48 h later received intramyocardial injection of vehicle (Vehicle, n=8), unfractionated MSCs (MSCs, n=8), or CD105- MSCs (CD105- MSCs, n=6). Echocardiography was performed 4 d prior to coronary occlusion/reperfusion (BSL1) and at 48 h (BSL2) and 35 d after cell injection. Mice were sacrificed at 35 d. LV ejection fraction (EF) was significantly and similarly reduced in all groups at 48 h after MI (Figure). At 35 d after MI, mice injected with CD105- MSCs exhibited greater EF (Figure) and smaller LV end-diastolic volume compared with vehicle-treated and unfractionated MSC-treated mice. We conclude that compared with unfractionated MSCs, intramyocardial transplantation of CD105- MSCs after a reperfused MI results in improved cardiac repair. The use of this MSC subpopulation may potentially improve the outcomes of cell therapy in humans.