Platelet Rich Plasma (PRP) Produces an Atherofibrotic Histophenotype During Craniofacial Bone Repair Due to Changes of Immunohistochemical Expression of Erk1/2, p38α/β, Adiponectin and Elevated Presence of Cells Exhibiting B-scavenger Receptor (CD36+)

Abstract

The platelet-extracellular matrix interaction in platelet rich plasma (PRP) through thrombospondin receptor-CD36 induces the secretion of growth factors responsible for cellular proliferation and differentiation during the repair process. Since CD36 also acts as a class B-scavenger-receptor for development of foam-like cells and mitogen-activated kinases, such as Erk1/2 and p38α/β, are important proteins activated by platelet growth factor, the aim of this study was to evaluate the immunohistochemical presence of CD36, Erk1/2, p38α/β during the bone repair treated and non-treated with PRP and to compare these results with the histomorphometry of repair. Simultaneously, the immunopresence of adiponectin was analyzed, which may contribute to osteogenesis at the same time it inhibits fibrosis and impairs adipogenesis and foam cell formation in the medullary area. An artificial bone defect measuring 5×1 mm was produced in the calvaria of 56 Wistar rats. The defects were randomly treated with autograft, autograft+PRP, PRP alone and sham. The animals were euthanized at 2 and 6 weeks post-surgery. Data were analyzed by ANOVA followed by non-parametric test Student Newman-Keuls (p<0.05) for histomorphometric and immunohistochemical interpretation. The results revealed that in specimens that received PRP the immunopositivity for Erk1/2, p38α/β and CD36 proteins increased significantly while the immunohistochemical expression of adiponectin decreased simultaneously. There was also an accentuated reduction of bone matrix deposition and increase of the medullary area represented by fibrosis and/ or presence of foam-like cells, which exhibited immunophenotype CD36+adiponectin. The findings of this study suggest that PRP acted as an inhibitor of osteogenesis during the craniofacial bone repair and induced a pathological condition that mimics an atherofibrotic condition.

Platelet-Rich Plasma Prevents In Vitro Transforming Growth Factor-β1-Induced Fibroblast to Myofibroblast Transition: Involvement of Vascular Endothelial Growth Factor (VEGF)-A/VEGF Receptor-1-Mediated Signaling †

“…However, the antifibrotic potential of PRP is still controversial. Indeed some reports show limited effectiveness or inefficacy of this blood-derived product in counteracting the fibrotic response [ 46 , 47 , 48 , 49 ], or even a fibrosis development after PRP treatment [ 35 , 50 , 51 , 52 ].…”

Platelet-Rich Plasma and Bone Marrow-Derived Mesenchymal Stromal Cells Prevent TGF-β1-Induced Myofibroblast Generation but Are Not Synergistic when Combined: Morphological in vitro Analysis

“…It must, however, be pointed out that many critical issues related to the clinical application of both PRP and MSCs still exist. PRP criticisms are mainly represented by the heterogeneity of formulations, owing to the different non-standardized preparation procedures and by the lack of univocal guidelines for the best usage with respect to dose, optimal timing of administration, frequency and customization for targeted tissues, which may account for the reported conflicting results concerning the effects of this blood product in the modulation of tissue fibrosis [Delos et al, 2014;Cianforlini et al, 2015;Kelc and Vogrin, 2015;Reurink et al, 2015;Vu et al, 2015;Guillodo et al, 2016;Lynch and Bashir, 2016;Schroeder et al, 2016;Moghadam et al, 2017;Jang et al, 2017;Sanchez-Avila et al, 2018;Sayadi et al, 2018;Shoeib et al, 2018;Tavukcu et al, 2018;Chellini et al, 2019]. On the other hand, it is worth reminding that a single biomarker or a reliable combination of biomarkers that specifically and/or exclusively define bone marrow MSCs, are still unidentified, thus leading to the risk of getting a not homogeneous cell culture, even contaminated by non-mesenchymal cells.…”

Platelet‐rich plasma affects gap junctional features in myofibroblasts in vitro via vascular endothelial growth factor (VEGF)‐A/VEGF receptor

“…Increasing evidence supports the antifibrotic potential of platelet‐rich plasma (PRP) (Moghadam et al., 2017; Shoeib et al., 2018; Vu et al., 2015), a plasma preparation with a platelet concentration > 2.0 × 10 6 cells/μL, representing a storage vehicle of several bioactive molecules (Chellini et al., 2019). However, the effects of PRP are still controversial and the mechanisms underpinning its action are not fully clarified, calling into question its clinical application for antifibrotic purposes (Guillodo et al., 2016; Lynch & Bashir, 2016; Schroeder et al., 2016).…”