Peripheral blood mononuclear cells (PBMCs) contain a cell fraction of mononuclear progenitor cells (MPCs), which own significant angiogenic potential. Autologous transplant of PBMC and/or platelet-rich plasma (PRP) promotes endothelial cells differentiation in experimental lower limb ischemia, which is considered a safe and effective strategy to support revascularization, either in animal models or clinical trials. In addition, thrombin has been proposed to enrich biological scaffolds, hence increasing MPC viability after intramuscular administration, whereas proangiogenic mediators such as vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF-α), inhibitor of the plasminogen activator-1 (PAI-1), and chemokine (CXCL1; GRO-α) participate in the endothelial response to ischemia, through their proangiogenic effects over endothelial cells proliferation, survival, migration, endothelial integrity maintenance, and physiologic vascular response to injury. In the present study, we describe the effect of autologous PBMCs transplant and PRP, either with or without thrombin, over proangiogenic mediators (measured by enzyme-linked immunosorbent assay) and revascularization response (angiographic vascular pattern at 30 days after vascular occlusion) in a rat model of lower limb ischemia. The group treated with PBMC + PRP significantly induced PAI-1, an effect that was prevented by the addition of thrombin. Furthermore, treatment with PBMC + PRP + thrombin resulted in the induction of VEGF. GRO-α showed a sensitive induction of all proangiogenic mediators. All treatments significantly stimulated revascularization, according to angiographic assessment, whereas higher effect was observed with PBMC + PRP treatment (p < .0001). In conclusion, autologous PBMC transplant stimulates revascularization during experimental ischemia of the lower limb, whereas particular effects over proangiogenic and fibrinolytic mediators may be attributed to PBMCs and its combination with PRP and thrombin.

中文翻译：

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自体移植外周血单核细胞与促血管生成因子在下肢缺血性血运重建中的作用。

外周血单核细胞（PBMC）包含单核祖细胞（MPC）的细胞级分，它们具有显着的血管生成潜力。PBMC和/或富血小板血浆（PRP）的自体移植可促进实验性下肢缺血中的内皮细胞分化，在动物模型或临床试验中，这被认为是支持血运重建的安全有效策略。另外，已提出凝血酶可富集生物支架，从而增加肌肉内给药后MPC的活力，而促血管生成介质，例如血管内皮生长因子（VEGF），肿瘤坏死因子α（TNF-α），纤溶酶原激活物1的抑制剂（PAI-1）和趋化因子（CXCL1;GRO-α）参与了对缺血的内皮反应，通过其对血管内皮细胞增殖，存活，迁移，内皮完整性维持以及对损伤的生理性血管反应的促血管生成作用。在本研究中，我们描述了在有或没有凝血酶的情况下，自体PBMCs移植和PRP对促血管生成介质（通过酶联免疫吸附测定法测量）和血运重建反应（血管阻塞后30天的血管造影血管模式）的影响下肢缺血大鼠模型。用PBMC + PRP治疗的组可明显诱导PAI-1，但凝血酶的添加可阻止这种作用。此外，PBMC + PRP +凝血酶治疗可诱导VEGF。GRO-α显示所有促血管生成介质的敏感诱导。所有治疗均显着刺激血运重建，根据血管造影评估，而PBMC + PRP治疗观察到更高的效果（p <.0001）。总之，自体PBMC移植可在下肢实验性缺血期间刺激血运重建，而对促血管生成和纤溶介质的特殊作用可能归因于PBMC及其与PRP和凝血酶的结合。