Selectively activated PRP exerts differential effects on tendon stem/progenitor cells and tendon healing

Abstract

To understand the variable efficacy with platelet rich plasma (PRP) treatments for tendon injury, we determined the differential effects of proteinase-activated receptor (PAR)1- or PAR4-activated PRP (PAR1-PRP, PAR4-PRP) from humans on human patellar tendon stem/progenitor cells (TSCs) and tendon healing. We show that PAR1-PRP released VEGF, whereas PAR4-PRP released endostatin. Treatment of TSCs with PAR1-PRP increased collagen I expression and matrix metalloproteinase-1 (MMP-1), but cells treated with PAR4-PRP increased less collagen I and higher MMP-2 expression. The wound area treated with PAR4-PRP formed tendon-like tissues with well-organized collagen fibers and fewer blood vessels, while PAR1-PRP treatment resulted in the formation of blood vessels and unhealed tissues. These findings indicate that differential activation of PRP leads to different effects on TSCs and tendon healing. We suggest that based on acute or chronic type of tendon injury, selective activation of PRP should be applied in clinics in order to treat injured tendons successfully.

In vitro responses to platelet-rich-plasma are associated with variable clinical outcomes in patients with knee osteoarthritis

“…It is believed that platelets, which contain and release numerous growth factors, promote healing, dampen inflammation, and reduce pain 3 – 5 . These blood-derived products have been used to enhance chondrogenesis 6 , 7 , treat bone 8 , 9 , tendon 10 , 11 and ligament 12 , 13 injuries, and have recently emerged as a potential therapeutic for knee OA 14 .…”

Effects and mechanisms of basic fibroblast growth factor on the proliferation and regenerative profiles of cryopreserved dental pulp stem cells

“…Some studies have shown that many growth factors including the human recombinant growth factors (eg, basic fibroblast growth factor, bFGF) 9,10 and the autogenous growth factors (eg, platelet‐rich plasma, PRP or platelet lysate, PL) 10‐12 have ability to affect the biology properties of MSCs. Among them, PRP or PL is a blood‐derived concentrate with a combination of growth factors, and has been confirmed to promote the proliferation and differentiation of stem cells 11‐13 . However, the products of PRP or PL display a number of disadvantages, and for instance, the preparation procedure is very complex and expensive, the composition may vary according to the different patients and preparation methods, and the mechanism and mainly responsible factors’ effect on stem cells have not been clear 10,13 .…”

Platelet-Rich Plasma Therapy in the Treatment of Diseases Associated with Orthopedic Injuries

“…77 Due to poor blood supply and limited self-renewal, injured tendons and ligaments heal slowly and incompletely. 78 The multistage healing procedure of cell proliferation and ECM production is slow and leads to the formation of collagenrich scar tissue with undesirable mechanical properties that make healed tendons susceptible to reinjury. 78 In addition, chronic pain, weakness, activity limitations, and loss of stamina 79 decrease the quality of life.…”

“…Previous studies have demonstrated that activated PRP can stimulate the proliferation of TSCs and the production of tenocytes and abundant collagen. 78 Kim et al 80 investigated the therapeutic effect of bone marrow aspirate concentrates (BMACs) combined with PRP and tendon-derived stem cells (TDSCs) for rotator cuff tendon tears. The results indicated that the proliferation and migration of TDSCs were enhanced by the combination treatment and that the aberrant osteogenic and chondrogenic differentiation of TDSCs was prevented.…”

“…2 Zhang et al showed that different types of activation of PRP result in different effects on TSCs and tendon healing, suggesting that activated PRP should be applied in clinics to treat various types of tendon injury. 78 To date, a single application of PRP in both animal studies and clinical trials for ligament, muscle, and tendon injuries has resulted in a variety of outcomes. In a controlled study with a rat model, Beck et al 81 found that PRP altered the tissue properties of tendons and decreased tendon tissue stiffness without affecting the construct's failure load.…”