Effect of autologous transplant of peripheral blood mononuclear cells in combination with proangiogenic factors during experimental revascularization of lower limb ischemia

Abstract

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

Current Status of Angiogenic Cell Therapy and Related Strategies Applied in Critical Limb Ischemia

“…Li et al made a comparison between CD34+ and CD34-cells in PB-MNCs, concluding that both induce neovascularization, but only CD34+ incorporate into new capillaries [89]. PB-MNCs promote revascularization in ischemic limbs, even more when they are combined with platelet-rich plasma (PRP) [90]. PRP, a source of platelets, cytokines, and growth factors, participates in ECs proliferation and differentiation, interacting with important cell receptors related with angiogenesis [90].…”

“…PB-MNCs promote revascularization in ischemic limbs, even more when they are combined with platelet-rich plasma (PRP) [90]. PRP, a source of platelets, cytokines, and growth factors, participates in ECs proliferation and differentiation, interacting with important cell receptors related with angiogenesis [90]. Furthermore, in order to achieve high stem cell concentrations, hematopoietic growth factors are frequently used to induce cell mobilization.…”

Understand the role of exosomal miRNA in the development of breast cancer in patients with chronic HBV infection

“…Whether this change will affect the overall expression of CXCL12 in breast tissue needs to be further investigated. CXCL1, a small chemokine belonging to the CXC chemokine family, was closely related to in ammation [74] , angiogenesis [75] , tumor formation [76] and so on. CXCL1 can promote the invasion and metastasis of breast cancer cells by activating ERK to promote the expression of MMP2/9 [77] .Breast cancer cells promote CXCL1/S100A8/9 survival axis through high expression of TNF-α to promote breast cancer cells to resist chemotherapy [78] .…”