Platelet rich plasma extract promotes angiogenesis through the angiopoietin1-Tie2 pathway

Abstract

Development and regeneration of tissues and organs require precise coordination among endothelial, epithelial and mesenchymal morphogenesis. Angiogenesis plays key roles in normal development, wound healing, recovery from ischemic disease, and organ regeneration. It has been recognized that the combination of various angiogenic factors in an appropriate physiological ratio is critical for long-term functional blood vessel formation. Here we show that mouse soluble platelet-rich-plasma (PRP) extract, which includes abundant angiopoetin-1 (Ang1) and other angiogenic factors, stimulates endothelial cell growth, migration and differentiation in cultured human dermal microvascular endothelial cells in vitro and neonatal mouse retinal angiogenesis in vivo. Mouse platelet rich fibrin (PRF) matrix, the three-dimensional fibrin matrix that releases angiogenic factors with similar concentrations and proportions to the PRP extract, also recapitulates robust angiogenesis inside the matrix when implanted subcutaneously on the living mouse. Inhibition of Ang1-Tie2 signaling suppresses PRP extract-induced angiogenesis in vitro and angiogenic ability of the PRF matrix in vivo. Since human PRP extract and PRF matrix can be prepared from autologous peripheral blood, our findings may lead to the development of novel therapeutic interventions for various angiogenesis-related diseases as well as to the improvement of strategies for tissue engineering and organ regeneration.

Keywords: 3D; ARDS; Ang; BrdU; D-HMVE; EBM2; EC; ECM; ELISA; FDA; Food and Drug Administration; H&E; IF; IP; PD-EGF; PDGF; PDMS; PRF; PRP; TGF-β; VEGF; VEGFR2; acute respiratory distress syndrome; angiopoietin; b-FGF; basic fibroblast growth factor; bromodeoxyuridine; conA; concanavalin-A; endothelial basal medium-2; endothelial cell; enzyme-linked immunosorbent assay; extracellular matrix; hematoxylin and eosin; human dermal microvascular endothelial; immunofluorescence; intraperitoneal; platelet rich fibrin; platelet rich plasma; platelet-derived epidermal growth factor; platelet-derived growth factor; polydimethylsiloxane; qRT-PCR; quantitative reverse transcription polymerase chain reaction; three dimensional; transforming growth factor beta; vascular endothelial growth factor; vascular endothelial growth factor receptor 2.