Abstract 1023: Transplantation Of Bone Marrow-derived Very Small Embryonic-like Stem Cells (VSELs) Improves Left Ventricular Function And Remodeling After Myocardial Infarction
Adult bone marrow (BM) contains a rare population of pluripotent Sca-1+/Lin-/CD45- very small embryonic-like stem cells (VSELs) that differentiate into cardiomyocytes in vitro. The clinical usefulness of these primitive cells, however, is limited by their rarity, which makes it impossible to isolate a large number of VSELs for transplantation. Therefore, we examined if in vitro expansion followed by predifferentiation of VSELs in cardiomyogenic medium would enhance the cardiac reparative benefits of these cells. VSELs isolated from adult mouse BM were expanded in vitro; cardiac differentiation was induced by culturing expanded cells in a cardiomyogenic medium for 5 days. Mice underwent a 30-min coronary occlusion followed by reperfusion and, 48 h later, received intramyocardial injection of vehicle (group I, n = 11) or expanded VSELs (100,000 cells) without (group II, n = 8) or with (group III, n = 11) prediffer-entiation. At 35 d after MI, mice in group III exhibited improved LV ejection fraction (54.5 ± 3.3% vs. 41.5 ± 3.3% in group I, P<0.05) and infarct wall thickening fraction (51.5 ± 5.7% vs. 28.7 ± 4.5% in group I, P<0.05) (Fig⇓). VSEL transplantation also ameliorated postinfarct LV dilation as evidenced by a smaller LV end-diastolic volume (60.6 ± 5.4 μl vs. 79.8 ± 8.1 μl in group I, P<0.05) (Fig⇓). In contrast, transplantation of VSELs without predifferentiation (group II) failed to produce statistically significant benefits. We conclude that transplantation of expanded and predifferentiated VSELs improves LV remodeling and dysfunction after MI. Our results lay the groundwork for novel therapies based on the use of these pluripotent cells, which are present in normal adult BM.