Angiogenic Properties of ‘Leukocyte- and Platelet-Rich Fibrin’

Abstract

Leukocyte- and Platelet-Rich Fibrin (L-PRF) is an autologous platelet concentrate, consisting of a fibrin matrix enriched with platelets, leukocytes and a plethora of cytokines and growth factors. Since L-PRF is produced bedside from whole blood without the use of an anti-coagulant, it is becoming a popular adjuvant in regenerative medicine. While other types of platelet concentrates have been described to stimulate blood vessel formation, little is known about the angiogenic capacities of L-PRF. Therefore, this study aimed to fully characterize the angiogenic potential of L-PRF. With an antibody array, the growth factors released by L-PRF were determined and high levels of CXC chemokine receptor 2 (CXCR-2) ligands and epidermal growth factor (EGF) were found. L-PRF induced in vitro key steps of the angiogenic process: endothelial proliferation, migration and tube formation. In addition, we could clearly demonstrate that L-PRF is able to induce blood vessel formation in vivo, the chorioallantoic membrane assay. In conclusion, we could demonstrate the angiogenic capacity of L-PRF both in vitro and in vivo, underlying the clinical potential of this easy-to-use platelet concentrate.

Therapeutic Potential of Dental Pulp Stem Cells and Leukocyte- and Platelet-Rich Fibrin for Osteoarthritis

“…In addition, MCP-1 increased MMP-13 expression in chondrocytes [86]. Furthermore, several other proteins that are abundantly present in L-PRF CM, such as RANTES, growth regulated oncogene (GRO) and IL-8 might be responsible for the observed effects in our study [31]. RANTES is demonstrated to induce chondrocyte expression of inducible NO synthase, IL-6 and MMP-1 [87], while IL-8 and GROα are shown to induce articular chondrocyte hypertrophy and calcification through increased type X collagen, MMP-13 expression and alkaline phosphatase activity [88].…”

“…Several growth factors, such as VEGF, EGF, IL-6 and MCP-1, are highly present in L-PRF CM and in minor levels in the exudate [31,64] and might be accountable for the observed effects in the present study. For example, VEGF is reported to act as a survival factor in growth plate chondrocytes and has proliferative effects in immortalised chondrocytes [78].…”

“…anti-microbial properties [59]), but might at the same time be involved in catabolic pathways [60]. Moreover, the leukocyte fraction in L-PRF has been reported to be accountable for the overproduction of several growth factors, including VEGF and inflammatory cytokines [59,61], which have been described to negatively impact chondrogenesis in vitro [31,[62][63][64][65][66][67]. In contrast, many other growth factors present in L-PRF ex and L-PRF CM are reported to have beneficial influences on MSC chondrogenesis [31,34,68,69].…”

“…This alteration in outcome between the two L-PRF derivatives might be explained in the difference in growth factor levels. Specifically, significantly higher levels of growth factors are found in L-PRF CM compared to L-PRF ex, which can be caused by the fact that L-PRF CM is generated after incubation for 96 h, resulting in a continuous release of growth factors by the leukocytes in the fibrin matrix of the L-PRF [26,31]. RT-qPCR data demonstrated at 24 h post-stimulation a significant decrease in aggrecan and collagen type II α 1 mRNA levels of healthy iMACs when cultured in the presence of L-PRF CM.…”

Effect of platelet-rich fibrin on cell proliferation, migration, differentiation, inflammation, and osteoclastogenesis: a systematic review of in vitro studies

“…These observations were reproduced in embryonic kidney fibroblasts and in various cell lines such as HEK293, MG-63 osteosarcoma cells, human oral keratinocytes, SIRC, and 3T3 cells [18]. Mesenchymal cells, endothelial cells [23,42,55,63], epithelial cells [22], and macrophages [69] also responded to PRF with increasing proliferation. In contrast, PRF failed to induce proliferation of L929 fibroblasts [53] and human mesenchymal stem cells on collagen scaffolds [17].…”