Platelet Activation by Collagen Provides Sustained Release of Anabolic Cytokines

Abstract

Background Platelet-rich plasma (PRP) has been increasingly used in sports medicine applications. Platelets are thought to release growth factors important in wound healing, including transforming growth factor (TGF-β1), platelet-derived growth factor (PDGF-AB), and vascular endothelial growth factor (VEGF). However, little is known about the effect of platelet activator choice on growth factor release kinetics. Hypothesis The choice of platelet activator would affect the timing and level of growth factor release from PRP. Study Design Controlled laboratory study. Methods Platelet-rich plasma aliquots were activated with either thrombin or collagen. A control group of whole blood aliquots was clotted with thrombin. Supernatant containing the released growth factors was collected daily for 1 week. Levels of TGF-β1, PDGF-AB, and VEGF were measured using enzyme-linked immunosorbent assay (ELISA). Results The use of thrombin as an activator resulted in immediate release of TGF-β1 and PDGF-AB, while the collagen-activated PRP clots released similar amounts each day for 5 days. The use of collagen as an activator resulted in an 80% greater cumulative release of TGF-β1 from the PRP aliquots over 7 days (P < .001). Concentrating platelets to 3 times the systemic blood level resulted in a 3-fold higher release of TGF-β1, 2.5-fold greater release of PDGF, and 5-fold greater release of VEGF (all P < .0001) when compared with whole blood control clots, but no significant differences in the timing of release were noted. Conclusion These experiments demonstrated that the choice of platelet activator can significantly influence the release kinetics of cytokines from PRP, with thrombin resulting in an immediate release and collagen having a more sustained release pattern. Clinical Relevance The level and rate of growth factor release depends on the selected platelet activator, a factor that should be considered when selecting a PRP system for a given application.

Platelets Promote Mitochondrial Uncoupling and Resistance to Apoptosis in Leukemia Cells: A Novel Paradigm for the Bone Marrow Microenvironment

“…5e). Although platelets have been shown to release significant amounts of TGFβ1 [27], the observed effects of SP on ΔΨM were insensitive to pharmacological treatment with the potent and specific inhibitor of the TGFβ receptor superfamily, SB-431542 (Fig. 5f).…”

Emerging Potential of Cell Based Therapies for Articular Cartilage Repair and Regeneration

“…Intra-articular injections of PRP are given to the patients, these platelets are activated by endogenous thrombin and/or intra-articular collagen. 110 Once activated, there is secretion of growth factors by degranulation of the alpha granules. 111 Platelet-derived growth factor (PDGF), interleukin-1 receptor antagonist (IL-1RA), soluble receptor of tumor necrosis factor α (TNF-RI), transforming growth factor β (TGF-β), platelet factor 4 (PF4), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), insulin-like growth factor (IGF), osteocalcin (Oc), osteonectin (On), fibrinogen, vitronectin, fibronectin and thrombospondin-1 (TSP-1)are among the secreted substances.…”

“…The antagonist of IL-1 receptor inhibits activation of NFkB gene which regulates the cytokine involved in apoptosis and inflammation process. 110,113 Moreover, the soluble receptors of the tumor necrosis factor bind to TNF-α, preventing its interaction with cellular receptors and its pro-inflammatory signaling. TGF-β 1 also acts as a factor inhibiting cartilage degradation, regulating and enhancing gene expression of tissue inhibitors of metalloproteinases (TIMP-1).…”

2011 AOA Symposium: Tissue Engineering and Tissue Regeneration

“…Collagen also is a substrate that encourages cell migration within the scaffold 68 . Lastly, collagen is a known activator of platelets and results in a more physiological and sustained release of growth factors from platelets in comparison with that seen with thrombin-based techniques 69,70 . Thus, one possible biomaterial that could be used for intraarticular healing is a collagen-platelet composite scaffold.…”