Platelet Lysate Inhibits NF-κB Activation and Induces Proliferation and an Alert State in Quiescent Human Umbilical Vein Endothelial Cells Retaining Their Differentiation Capability

Abstract

: Injured blood vessel repair and blood circulation re-establishment are crucial events for tissue repair. We investigated in primary cultures of human umbilical vein endothelial cells (HUVEC), the effects of platelet lysate (PL), a cocktail of factors released by activated platelets following blood vessel disruption and involved in the wound-healing process triggering. PL exerted a protective effect on HUVEC in an inflammatory milieu by inhibiting IL-1α-activated NF-κB pathway and by inducing the secretion of PGE2, a pro-resolving molecule in the wound microenvironment. Moreover, PL enhanced HUVEC proliferation, without affecting their capability of forming tube-like structures on matrigel, and activated resting quiescent cells to re-enter cell cycle. In agreement with these findings, proliferation-related pathways Akt and ERK1/2 were activated. The expression of the cell-cycle activator Cyclin D1 was also enhanced, as well as the expression of the High Mobility Group Box-1 (HMGB1), a protein of the alarmin group involved in tissue homeostasis, repair, and remodeling. These in vitro data suggest a possible in vivo contribution of PL to new vessel formation after a wound by activation of cells resident in vessel walls. Our biochemical study provides a rationale for the clinical use of PL in the treatment of wound healing-related pathologies.

The Effect of a Polyester Nanofibrous Membrane with a Fibrin-Platelet Lysate Coating on Keratinocytes and Endothelial Cells in a Co-Culture System

“…Thus, the presence of the von Willebrand factor after 7 days of culturing indicated that the co-culture containing keratinocytes and NF membranes did not interfere with the endothelial cell maturation process. These results are in agreement with those of other authors who indicated that PL acts to enhance endothelial cell proliferation without affecting their differentiation capacity [ 51 ].…”

Platelet Lysate Induces in Human Osteoblasts Resumption of Cell Proliferation and Activation of Pathways Relevant for Revascularization and Regeneration of Damaged Bone

“…Indeed, VEGF is playing a significant role both in osteoblasts differentiation and in the angiogenesis induction [ 29 , 47 , 48 ]. Moreover, in a recent publication, we reported that PL has a direct effect on endothelial cells by inducing their proliferation while maintaining their differentiation potential [ 22 ].…”

“…We reported that the platelet factors promoted the activation of the cell proliferation machinery and the cell-cycle re-entry of several types of cells, including chondrocytes and chondroprogenitors [ 18 , 19 , 20 ], human umbilical vein endothelial cells [ 21 , 22 ], bone marrow and umbilical cord mesenchymal stromal cells (MSCs) [ 21 , 23 ], adipose tissue cells [ 21 , 23 , 24 ], and amniotic fluid cells [ 25 ].…”

Functionalising Collagen-Based Scaffolds With Platelet-Rich Plasma for Enhanced Skin Wound Healing Potential

“…The effects of the released factors were evaluated for both our composite scaffold and PRP releasate (PRPr) in different cell types (endothelial, mesenchymal stromal cells, macrophages, fibroblasts, and keratinocytes) since all of them have key roles during different stages of wound healing (Gurtner et al, 2008;Eming et al, 2014). There is vast literature suggesting that PRP supports endothelial cell proliferation and induces angiogenesis/vascularization both in vitro and in vivo (Kakudo et al, 2014;Anitua et al, 2015;Notodihardjo et al, 2015;Etulain et al, 2018;Romaldini et al, 2019;Samberg et al, 2019). Our work corroborates those findings, but, importantly, shows that this activity is maintained within a biomaterial scaffold with proven regenerative potential.…”