Biology of platelet-rich plasma and its clinical application in cartilage repair
Xuetao Xie
0
1
Changqing Zhang
1
Rocky S Tuan
0
0
Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine
,
Pittsburgh, PA 15219
,
USA
1
Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University School of Medicine
,
Shanghai 200233
,
China
Platelet-rich plasma (PRP) is an autologous concentrated cocktail of growth factors and inflammatory mediators, and has been considered to be potentially effective for cartilage repair. In addition, the fibrinogen in PRP may be activated to form a fibrin matrix to fill cartilage lesions, fulfilling the initial requirements of physiological wound healing. The anabolic, anti-inflammatory and scaffolding effects of PRP based on laboratory investigations, animal studies, and clinical trials are reviewed here. In vitro, PRP is found to stimulate cell proliferation and cartilaginous matrix production by chondrocytes and adult mesenchymal stem cells (MSCs), enhance matrix secretion by synoviocytes, mitigate IL-1-induced inflammation, and provide a favorable substrate for MSCs. In preclinical studies, PRP has been used either as a gel to fill cartilage defects with variable results, or to slow the progression of arthritis in animal models with positive outcomes. Findings from current clinical trials suggest that PRP may have the potential to fill cartilage defects to enhance cartilage repair, attenuate symptoms of osteoarthritis and improve joint function, with an acceptable safety profile. Although current evidence appears to favor PRP over hyaluronan for the treatment of osteoarthritis, the efficacy of PRP therapy remains unpredictable owing to the highly heterogeneous nature of reported studies and the variable composition of the PRP preparations. Future studies are critical to elucidate the functional activity of individual PRP components in modulating specific pathogenic mechanisms.
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Introduction
Cartilage injuries are a common clinical challenge and
affect 27 million people in the United States, resulting in
208,600 primary total hip replacement and 450,000 primary
total knee replacements, according to data for 2005 [1,2].
The number of total hip replacement and total knee
replacement operations is expected to reach 572,000
and 3,480,000, respectively, by 2030 [1].
In the past decade, platelet-rich plasma (PRP) has
emerged as a non-operative treatment modality for
cartilage injuries [3,4]. The rationale for its use is largely
dependent on its functional components (Figure 1).
While there are significant variations in its makeup, the
initial PRP consistently contains highly concentrated
platelets and a number of plasma proteins associated
with platelets during its preparation by centrifugation.
Platelets are produced by megakaryocytes as
anucleated cells [5]. A variety of growth factors, coagulation
factors, adhesion molecules, cytokines, chemokines and
integrins are stored in platelets [6-8]. After activation,
the platelets in PRP can release a multitude of growth
factors at concentrations significantly higher than the
baseline blood levels, including transforming growth
factor-, platelet-derived growth factor (PDGF),
insulinlike growth factor (IGF), basic fibroblast growth factors,
vascular endothelial growth factor (VEGF), epidermal
growth factors, and many others [9]. Many of these
anabolic cytokines, such as transforming growth factor-,
IGF, basic fibroblast growth factor and PDGF, are
chondro-promoting and chondro-protective [10-13].
Specifically, they can stimulate chondrocyte and
multipotent mesenchymal stem cell (MSC) proliferation,
promote chondrocyte synthesis of aggrecan and collagen
type II (Col II), drive MSC chondrogenic differentiation,
prevent chondrocyte and MSC apoptosis, and diminish
the catabolic effects of inflammatory cytokines, such as
IL-1, and matrix metalloproteinases (MMPs).
Platelets in PRP are also a source of inflammatory
mediators and modulators. After incubation with polyacrylamide
beads, platelets may release numerous anti-inflammatory
cytokines, including IL-1 receptor antagonist (IL-1ra),
Figure 1 Principal components and potential effects and actions
of PRP. PRP contains growth factors that stimulate cellular anabolism,
inflammatory mediators and modulators that exert anti-inflammatory
effects, and fibrinogen that acts as a biomaterial scaffold. PRP,
platelet-rich plasma.
soluble tumor necrosis factor (TNF) receptor (sTNF-R)
I and II, IL-4, IL-10, IL-13, and interferon [14].
Specifically, IL-1ra inhibits the bioactivity of IL-1 by blocking
its receptors [15,16]. sTNF-RI and sTNF-RII can bind to
free TNF, thereby preventing signal transduction
[15,16]. IL-4, IL-10 and IL-13 can increase IL-1ra
production and reduce TNF-induced prostaglandin E2
production [17,18]. Interferon induces the production
of IL-18-binding protein, a natural inhibitor of IL-18
[19]. Although PRP also releases pro-inflammatory
cytokines, such as I (...truncated)