Angiogenesis by Implantation of Peripheral Blood Mononuclear Cells and Platelets Into Ischemic Limbs

Abstract

Background-Peripheral PϽ0.01). Neocapillary densities were increased by implantation of PBMNCsϩplatelets or platelets alone (3.5-fold and 2.4-fold, respectively; PϽ0.001), whereas PMNs inhibited (32%, PϽ0.05) PBMNCϩplatelet-mediated capillary formation. There was no incorporation of implanted PBMNCs into neocapillaries, whereas PBMNCs and platelets accumulated around arterioles after implantation. Cellular extract from PBMNCsϩplatelets, in which vascular endothelial growth factor (VEGF), basic fibroblast growth factor, platelet-derived growth factor-AB, and transforming growth factor-␤ were detected, markedly stimulated tubule formation of human umbilical vein vascular endothelial cells. Anti-VEGF neutralizing antibody markedly inhibited tubule formation and in vivo vessel formation. Neutrophil elastase inhibitor blocked the antiangiogenic action of PMNs, whereas inhibitors of oxygen metabolites had no effect. Conclusions-This study demonstrated that implantation of PBMNCs and platelets into ischemic limbs effectively induces collateral vessel formation by supplying angiogenic factors (mainly VEGF) and cytokines, suggesting that this cell therapy is useful as a novel strategy for therapeutic angiogenesis.

Anti-metastatic effects of antrodan, the Antrodia cinnamomea mycelia glycoprotein, in lung carcinoma cells

“…However, it should be noted that the levels of IL-12 and IL-1␤ levels in the antrodan CM are relatively low, although the levels of IL-12 are comparable to those ( 10 pg/mL of MNC-CM) reported by our group previously [3] where it was concluded that IL-12 contributes to the anti-angiogenic effects of polysaccharides from A. cinnamomea. The levels of IL-1␤ reported herein (2-8 pg/mL) are comparable or even higher than those (20 ± 4 pg/5 mL MNC-CM or roughly 4 pg/mL) reported by Iba et al [30] in which much higher number of MNCs (1 × 10 7 cells) than the present study (5 × 10 5 MNCs) was used. Nonetheless, further studies are needed to confirm that these levels of IL-12 and IL-1␤ are able to affect the metastatic activities of LLC.…”

Improved Arteriogenesis with Simultaneous Skeletal Muscle Repair in Ischemic Tissue by SCL+ Multipotent Adult Progenitor Cell Clones from Peripheral Blood

“…Consistent with this is the observation that impaired recruitment of bone marrow-derived stem cells interferes with successful angiogenesis [33]. This is in contrast to the study by Iba et al [34], who injected peripheral blood-derived monocytes along with platelets directly into the ischemic limb. Also Ziegelhoeffer et al [28]reported recently that bone marrow-derived cells do not incorporate into adult growing vasculature, unless they become part of tumor neoangiogenesis [28].…”

Hypoxia Inducible Factor-1α, Endothelial Progenitor Cells, Monocytes,Cardiovascular Risk, Wound Healing, Cobalt and Hydralazine:A Unifying Hypothesis

“…While the injection of human monocytes and platelets enhances neovascularization and increases capillary density in a rat hindlimb ischemia model, the addition of polymorphonuclear leukocytes to the cellular injectate abrogates the neovascular response [42]. Also, cultured lymphocytes, unlike cultured monocytes do not express endothelial cell markers with time [43] and unlike mononuclear cells, lymphocytes are not recruited to sites of VEGF-induced angiogenesis [44].…”

“…Whether putative bone marrow cells are found to be 'incorporated' into the vasculature may also be a function of the time of assessment since some investigators have shown that these cells originally accumulate in the interstitium and 'incorporate' into vessels by 2 weeks in a murine ischemic wound model [61]. Indeed, while many independent investigators have shown bone marrow cells to incorporate into the vasculature, there are a few reports that bone marrow cells do not incorporate into the vasculature and instead form periadventitial accumulations where they express angiogenic/ arteriogenic cytokines such as VEGF and fibroblast growth factor (FGF) [42,62,63]. This may represent different cell populations within the mononuclear fraction.…”