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

Division of Cardiovascular Research, St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Mass 02135, USA.
Circulation (Impact Factor: 14.95). 11/2006; 114(20):2163-9. DOI: 10.1161/CIRCULATIONAHA.106.644518
Source: PubMed

ABSTRACT 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).
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), 5x10(5) CD34+ cells/kg, 5x10(5) tMNCs/kg (low-dose MNCs [loMNCs]), or a higher dose of tMNCs (hiMNCs) containing 5x10(5) 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 mm2) than in the PBS, loMNC, and hiMNC groups (384.7+/-11.0, 372.5+/-14.1, and 497.5+/-24.0 per 1 mm2) (P<0.01). Percent fibrosis area on day 28 was less in the CD34(+) cell group (15.6+/-0.9%) than in the PBS, loMNC, 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, loMNC, 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, loMNC, and hiMNC groups (25.4+/-0.4, 24.9+/-0.4, and 24.1+/-0.6; P<0.05).
CD34+ cells exhibit superior efficacy for preserving myocardial integrity and function after MI than unselected circulating MNCs.


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