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

Tufts University, Бостон, Georgia, United States
Circulation (Impact Factor: 14.43). 11/2006; 114(20):2163-9. DOI: 10.1161/CIRCULATIONAHA.106.644518
Source: PubMed


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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Available from: Atsuhiko Kawamoto
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    • "However, it should be emphasized that the whole spectrum of bone-marrow derived CD34+ cells contains cell fractions that do not present functional characteristics of progenitor or of stem cells. Preclinical studies have shown that despite of their heterogeneity, human CD34+cells can stimulate neovascularization in ischemic myocardium by increasing capillary density and improving function in models of acute and chronic myocardial ischemia [7]. Clinical trials in the field of cardiovascular medicine also provided evidence that enriched pools of autologous CD34+ cells can improve clinical outcome results when administered by intramyocardial, intravascular, or intramuscular injection and supported further clinical development of this treatment strategy [8], [9]. "
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