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Kawamoto, A, Iwasaki, H, Kusano, K, Murayama, T, Oyamada, A, Silver, M et al.. CD34-positive cells exhibit increased potency and safety for therapeutic neovascularization after myocardial infarction compared with total mononuclear cells. Circulation 114: 2163-2169

Tufts University, Бостон, Georgia, United States
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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Available from: Atsuhiko Kawamoto, Aug 31, 2015
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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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    ABSTRACT: Circulating CD34+ progenitor cells () gained importance in the field of regenerative medicine due to their potential to home in on injury sites and differentiate into cells of both endothelial and osteogenic lineages. In this study, we analyzed the mobilization kinetics and the numbers of CD34+, CD31+, CD45+, and CD133+ cells in twenty polytrauma patients (n = 13 male, n = 7 female, mean age 46.5±17.2 years, mean injury severity score (ISS) 35.8±12.5 points). In addition, the endothelial differentiation capacity of enriched CD34+cells was assessed by analyzing DiI-ac-LDL/lectin uptake, the expression of endothelial markers, and the morphological characteristics of these cells in Matrigel and spheroid cultures. We found that on days 1, 3, and 7 after a major trauma, the number of CD34+cells increased from 6- up to 12-fold (p<0.0001) over the number of CD34+cells from a control population of healthy, age-matched volunteers. The numbers of CD31+ cells were consistently higher on days 1 (1.4-fold, p<0.01) and 7 (1.3-fold, p<0.01), whereas the numbers of CD133+ cell did not change during the time course of investigation. Expression of endothelial marker molecules in CD34+cells was significantly induced in the polytrauma patients. In addition, we show that the CD34+ cell levels in severely injured patients were not correlated with clinical parameters, such as the ISS score, the acute physiology and chronic health evaluation II score (APACHE II), as well as the sequential organ failure assessment score (SOFA-2). Our results clearly indicate that pro-angiogenic cells are systemically mobilized after polytrauma and that their numbers are sufficient for the development of novel therapeutic models in regenerative medicine.
    PLoS ONE 05/2014; 9(5):e97369. DOI:10.1371/journal.pone.0097369 · 3.23 Impact Factor
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    • "In our in vivo model of recovery from radiation induced myeloablation, different cell populations were transplanted into sublethally irradiated mice. It has been shown that transplanted ECs do not engraft in the BM [45], however, peripheral blood [46], [47], bone marrow [18]–[20], liver [48], [49] or lung [50] derived ECs have also been isolated in vitro and the transplanted ECs could restore impaired neovascularization in a hind limb ischemia [47], [51] or myocardial ischemia [52], [53] model. In our study the transplanted BM ECs were able to home and lodge in the BM, either at or adjacent to the vasculature. "
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    PLoS ONE 08/2013; 8(8):e67861. DOI:10.1371/journal.pone.0067861 · 3.23 Impact Factor
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    • "Advances and expansions have been made involving therapeutic effects of BM-derived stem and progenitor cells. Formerly, transdifferentiation into vasculature and/or cardiomyocytes was thought to be the predominant mechanism responsible for cardiac regeneration or repair [17, 20, 21, 39-47]; however, recent studies exposed such notions were overestimated [48-50] and that humoral or paracrine effects are the main mechanisms. The humoral mechanism benefits regeneration or restoration of myocardium and peripheral vascular tissues by inducing neovascularization, protecting ongoing cell apoptosis and degeneration, and promoting regeneration of endothelial cells, cardiomyocytes, and smooth muscle cells through soluble factors or cell-to-cell contact [42, 51-58]. "
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    06/2013; 48(2):76-86. DOI:10.5045/br.2013.48.2.76
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