Platelet-Rich Plasma Increases the Levels of Catabolic Molecules and Cellular Dedifferentiation in the Meniscus of a Rabbit Model

Abstract

Despite the susceptibility to frequent intrinsic and extrinsic injuries, especially in the inner zone, the meniscus does not heal spontaneously owing to its poor vascularity. In this study, the effect of platelet-rich plasma (PRP), containing various growth factors, on meniscal mechanisms was examined under normal and post-traumatic inflammatory conditions. Isolated primary meniscal cells of New Zealand white (NZW) rabbits were incubated for 3, 10, 14 and 21 days with PRP(−), 10% PRP (PRP(+)), IL(+) or IL(+)PRP(+). The meniscal cells were collected and examined using reverse-transcription polymerase chain reaction (RT-PCR). Culture media were examined by immunoblot analyses for matrix metalloproteinases (MMP) catabolic molecules. PRP containing growth factors improved the cellular viability of meniscal cells in a concentration-dependent manner at Days 1, 4 and 7. However, based on RT-PCR, meniscal cells demonstrated dedifferentiation, along with an increase in type I collagen in the PRP(+) and in IL(+)PRP(+). In PRP(+), the aggrecan expression levels were lower than in the PRP(−) until Day 21. The protein levels of MMP-1 and MMP-3 were higher in each PRP group, i.e., PRP(+) and IL(+)PRP(+), at each culture time. A reproducible 2-mm circular defect on the meniscus of NZW rabbit was used to implant fibrin glue (control) or PRP in vivo. After eight weeks, the lesions in the control and PRP groups were occupied with fibrous tissue, but not with meniscal cells. This study shows that PRP treatment of the meniscus results in an increase of catabolic molecules, especially those related to IL-1α-induced inflammation, and that PRP treatment for an in vivo meniscus injury accelerates fibrosis, instead of meniscal cartilage.

Platelet‐Rich Plasma (PRP) From Older Males With Knee Osteoarthritis Depresses Chondrocyte Metabolism and Upregulates Inflammation

“…A review of the literature on the chondrogenic effects of PRP in vitro, shows mixed results. Like our study, Lee et al, showed that 10% PRP increased the fibrous Col1a1 phenotype and decreased Col2a1 gene expression in meniscal cartilage from healthy young rabbits. In contrast, a study by Jeyakumar et al, showed that compared to 10% fetal calf serum, 10% PRP from healthy donors increased Col2a1 and decreased Col1a1 mRNA in human OA chondrocytes.…”

“…The increase in MMPs were significantly greater with H‐PRP and were not affected by the GF or inflammatory mediator grouping. Other studies have also shown that PRP upregulates MMPs, with the hypothesis being that the concentrated inflammatory cytokines (IL‐1β and TNF‐α) within PRP activates the known MMP pathways to stimulate remodeling . Research with APS made from PRP with increased concentrations of anti‐inflammatory proteins have been shown to reduce MMP‐13 production from chondrocytes stimulated with IL‐1β and TNF‐α .…”

A Prospective, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study Evaluating Meniscal Healing, Clinical Outcomes, and Safety in Patients Undergoing Meniscal Repair of Unstable, Complete Vertical Meniscal Tears (Bucket Handle) Augmented with Platelet-Rich Plasma

“…Therefore, it is believed that mesenchymal stem cells are necessary for repair of meniscus lesions in the avascular zone [ 12 ]. Additionally, in a recent article by Lee et al on a rabbit model of circular defect, PRP treatment failed to help in the production of meniscus cartilage, and it instead accelerated fibrosis and increased the production of catabolic molecules [ 48 ]. This might be a very important finding, as human studies have shown that catabolic activity in meniscus tissue may help identify patients who are at risk for progression of osteoarthritis following partial meniscectomy [ 49 ].…”

PRP in recurrent implantation failure, hope or hype? A Prospective randomized controlled study

“…It is collected from peripheral veins and contains several growth factors such as vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), platelet derived growth factor (PDGF), transforming growth factor (TGF) and other cytokines that stimulate proliferation and growth. Recently, PRP has been used in several medical conditions in ophthalmology, orthopedics, surgery and wound healing but it's efficacy in endometrial growth has not been fully elucidated [6,7,8,9,10,11,12] .…”