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


Por: Padilla, Luis, Arguero-Sanchez, Ruben, Rodriguez-Trejo, Juan Miguel, Carranza-Castro, Pilar Hazel, Suarez-Cuenca, Juan Antonio, Polaco-Castillo, Jaime, DiSilvio-Lopez, Mauricio, Lopez-Gutierrez, Javier, Olguin-Juarez, Horacio, Hernandez-Patricio, Alejandro, Vera-Gomez, Eduardo, Gomez-Calderon, Alan De Jesus, Tellez-Gonzalez, Mario Antonio, Mondragon-Teran, Paul

Publicada: 1 abr 2020
Resumen:
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-alpha), inhibitor of the plasminogen activator-1 (PAI-1), and chemokine (CXCL1; GRO-alpha) 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-alpha 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.

Filiaciones:
Padilla, Luis:
 Ctr Med Nacl 20 Noviembre, ISSSTE, Dept Expt Surg, Mexico City, DF, Mexico

Arguero-Sanchez, Ruben:
 Univ Nacl Autonoma Mexico, Fac Med, Dept Cirugia, Mexico City, DF, Mexico

Rodriguez-Trejo, Juan Miguel:
 Ctr Med Nacl 20 Noviembre, ISSSTE, Dept Angiol & Vasc Surg, Mexico City, DF, Mexico

Carranza-Castro, Pilar Hazel:
 Ctr Med Nacl 20 Noviembre, ISSSTE, Dept Expt Surg, Mexico City, DF, Mexico

Suarez-Cuenca, Juan Antonio:
 Ctr Med Nacl 20 Noviembre, ISSSTE, Lab Expt Metab & Clin Res, Mexico City, DF, Mexico

Polaco-Castillo, Jaime:
 Univ Nacl Autonoma Mexico, Fac Med, Dept Cirugia, Mexico City, DF, Mexico

DiSilvio-Lopez, Mauricio:
 Ctr Med Nacl 20 Noviembre, ISSSTE, Dept Expt Surg, Mexico City, DF, Mexico

Lopez-Gutierrez, Javier:
 Ctr Med Nacl 20 Noviembre, ISSSTE, Dept Expt Surg, Mexico City, DF, Mexico

Olguin-Juarez, Horacio:
 Ctr Med Nacl 20 Noviembre, ISSSTE, Dept Expt Surg, Mexico City, DF, Mexico

Hernandez-Patricio, Alejandro:
 Ctr Med Nacl 20 Noviembre, ISSSTE, Lab Expt Metab & Clin Res, Mexico City, DF, Mexico

Vera-Gomez, Eduardo:
 Ctr Med Nacl 20 Noviembre, ISSSTE, Lab Expt Metab & Clin Res, Mexico City, DF, Mexico

Gomez-Calderon, Alan De Jesus:
 Ctr Med Nacl 20 Noviembre, ISSSTE, Tissue Engn & Regenerat Med Res Grp, Mexico City, DF, Mexico

 Ctr Med Nacl 20 Noviembre, ISSSTE, Coordinac Invest, Mexico City, DF, Mexico

Tellez-Gonzalez, Mario Antonio:
 Ctr Med Nacl 20 Noviembre, ISSSTE, Tissue Engn & Regenerat Med Res Grp, Mexico City, DF, Mexico

 Ctr Med Nacl 20 Noviembre, ISSSTE, Coordinac Invest, Mexico City, DF, Mexico

Mondragon-Teran, Paul:
 Ctr Med Nacl 20 Noviembre, ISSSTE, Tissue Engn & Regenerat Med Res Grp, Mexico City, DF, Mexico

 Ctr Med Nacl 20 Noviembre, ISSSTE, Coordinac Invest, Mexico City, DF, Mexico
ISSN: 19326254
Editorial
WILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, Estados Unidos America
Tipo de documento: Article
Volumen: 14 Número: 4
Páginas: 600-608
WOS Id: 000527934300005
ID de PubMed: 32068332

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