Bone Grafts Research Today is a free monthly online journal that collates and summarizes the latest research about Bone Grafts, including details on spine fusion, surgery, procedure, risks. | ||||||||
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Sex-dependent attenuation of plaque growth after treatment with bone marrow mononuclear cells.Nelson WD, Zenovich AG, Ott HC, Stolen C, Caron GJ, Panoskaltsis-Mortari A, Barnes SA, Xin X, Taylor DA University of Minnesota, Minneapolis; R&D Systems, Minneapolis, MN 55455, USA. There are clinically relevant differences in symptomatology, risk stratification, and efficacy of therapies between men and women with coronary artery disease. Sex-based differences in plaque attenuation after administration of bone marrow mononuclear cells (BMNCs) are unknown. Forty-five male and 57 female apolipoprotein-E knockout (apoE(-/-)) mice were fed a high-fat diet. At 14 weeks of age, animals received 4 biweekly intravenous sex-matched (males, n=11; females, n=13) or -mismatched (males, n=12; females, n=14) BMNCs obtained from C57BL6/J mice. The rest of the apoE(-/-) mice were vehicle treated (males, n=13; females, n=20) or were age-matched untreated controls (males, n=9; females, n=10). Aortic plaque burden, progenitor cell profiles in bone marrow (BM) and 22 circulating cytokines/chemokines were examined 1 week following the final injection. Only female BMNCs infused into male apoE(-/-) recipients significantly decreased plaque formation (P<0.001). This reparative response univariately correlated with increased CD34(+) (P=0.02), CD45(+) (P=0.0001), and AC133(+)/CD34(+) (P=0.001) cell percentages in the BM of recipients but not with total serum cholesterol or percentage of BM-CD31(+)/CD45(low) cells. In a multivariate analysis, BM-AC133(+)/CD34(+) and BM-CD45(+) percentage counts correlated with a lower plaque burden (P<0.05). Increased granulocyte colony-stimulating factor levels highly correlated with plaque attenuation (r=-0.86, P=0.0004). In untreated apoE(-/-) mice of either sex, BM-AC133(+)/CD34(+) cells rose initially and then fell as plaque accumulated; however, BM-AC133(+)/CD34(+) percentages were higher in females at all times (P<or=0.01). We have demonstrated an atheroprotective effect of female-derived BMNCs administered to male atherosclerotic apoE(-/-) mice; this reparative response correlated with the upregulation of BM-AC133(+)/CD34(+) and CD45(+) cells and of circulating granulocyte colony-stimulating factor. Atherosclerotic female apoE(-/-) mice did not exhibit atheroprotection after BMNCs of either sex. Our findings may have implications for clinical cell therapy trials for coronary artery disease. Further exploration of sex-based differences in atheroprotection and vascular repair is warranted. Published 7 December 2007 in Circ Res, 101(12): 1319-27.
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