CD34-positive cells exhibit increased potency and safety for therapeutic neovascularization after myocardial infarction compared with total mononuclear cells

Background - We compared the therapeutic potential of purified mobilized human CD34(+) cells with that of mobilized total mononuclear cells (tMNCs) for the preservation/recovery of myocardial tissue integrity and function after myocardial infarction (MI). Methods and Results - CD34(+) cells were purified from peripheral blood tMNCs of healthy volunteers by magnetic cell sorting after a 5-day administration of granulocyte colony-stimulating factor. Phosphate-buffered saline (PBS), 5 x 10(5) CD34(+) cells/kg, 5 x 10(5) tMNCs/kg (low-dose MNCs [1oMNCs]), or a higher dose of tMNCs (hiMNCs) containing 5 x 105 CD34(+) cells/kg was transplanted intramyocardially 10 minutes after the induction of MI in athymic nude rats. Hematoxylin and eosin staining revealed that moderate to severe hemorrhagic MI on day 3 was more frequent in the hiMNC group than in the PBS and CD34(+) cell groups. Immunostaining for human-specific CD45 revealed abundant distribution of hematopoietic/inflammatory cells derived from transplanted cells in the ischemic myocardium of the hiMNC group. Capillary density on day 28 was significantly greater in the CD34(+) cell group (721.1 +/- 19.9 per 1 mm(2)) than in the PBS, 1oMNC, and hiMNC groups (384.7 +/- 11.0, 372.5 +/- 14.1, and 497.5 +/- 24.0 per 1 mm(2)) (P < 0.01). Percent fibrosis area on day 28 was less in the CD34(+) cell group (15.6 +/- 0.9%) than in the PBS, 1oMNC, and hiMNC groups (26.3 +/- 1.2%, 27.5 +/- 1.8%, and 22.2 +/- 1.8%) ( P < 0.05). Echocardiographic fractional shortening on day 28 was significantly higher in the CD34(+) cell group (30.3 +/- 0.9%) than in the PBS, 1oMNC, and hiMNC groups (22.7 +/- 1.5%, 23.4 +/- 1.1%, and 24.9 +/- 1.7%; P < 0.05). Echocardiographic regional wall motion score was better preserved in the CD34(+) cell group (21.8 +/- 0.5) than in the PBS, 1oMNC, and hiMNC groups (25.4 +/- 0.4, 24.9 +/- 0.4, and 24.1 +/- 0.6; P < 0.05). Conclusions - CD34(+) cells exhibit superior efficacy for preserving myocardial integrity and function after MI than unselected circulating MNCs.