The differential effects of leukocyte-containing and pure platelet-rich plasma (PRP) on tendon stem/progenitor cells - implications of PRP application for the clinical treatment of tendon injuries

Abstract

IntroductionPlatelet-rich plasma (PRP) is widely used to treat tendon injuries in clinics. These PRP preparations often contain white blood cells or leukocytes, and the precise cellular effects of leukocyte-rich PRP (L-PRP) on tendons are not well defined. Therefore, in this study, we determined the effects of L-PRP on tendon stem/progenitor cells (TSCs), which play a key role in tendon homeostasis and repair.MethodsTSCs isolated from the patellar tendons of rabbits were treated with L-PRP or P-PRP (pure PRP without leukocytes) in vitro, followed by measuring cell proliferation, stem cell marker expression, inflammatory gene expression, and anabolic and catabolic protein expression by using immunostaining, quantitative real-time polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay, respectively.ResultsCell proliferation was induced by both L-PRP and P-PRP in a dose-dependent manner with maximum proliferation at a 10 % PRP dose. Both PRP treatments also induced differentiation of TSCs into active tenocytes. Nevertheless, the two types of PRP largely differed in several effects exerted on TSCs. L-PRP induced predominantly catabolic and inflammatory changes in differentiated tenocytes; its treatment increased the expression of catabolic marker genes, matrix metalloproteinase-1 (MMP-1), MMP-13, interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α), and their respective protein expression and prostaglandin E2 (PGE2) production. In contrast, P-PRP mainly induced anabolic changes; that is, P-PRP increased the gene expression of anabolic genes, alpha-smooth muscle actin (α-SMA), collagen types I and III.ConclusionsThese findings indicate that, while both L-PRP and P-PRP appear to be “safe” in inducing TSC differentiation into active tenocytes, L-PRP may be detrimental to the healing of injured tendons because it induces catabolic and inflammatory effects on tendon cells and may prolong the effects in healing tendons. On the other hand, when P-PRP is used to treat acutely injured tendons, it may result in the formation of excessive scar tissue due to the strong potential of P-PRP to induce inordinate cellular anabolic effects.

Effect of intralesional platelet-rich plasma (PRP) treatment on clinical and ultrasonographic parameters in equine naturally occurring superficial digital flexor tendinopathies – a randomized prospective controlled clinical trial

“…MMPs and IL-1, that may influence tendon healing negatively [27, 73, 74], so that a low leucocyte content seems to be preferable to enhance anabolic effects during tendon healing.…”

PRP Treatment Efficacy for Tendinopathy: A Review of Basic Science Studies

“…This demonstrates that leukocytes can exacerbate inflammation in tendon cells but P-PRP without leukocytes can be anti-inflammatory because it decreased the gene expression of IL-6 when compared to untreated controls [39]. Similarly, PRP also reduced the gene expression and production of IL-6 in tendon cells when compared to cells treated with IL-1 β [50].…”

The use of platelet-rich plasma to augment conservative and surgical treatment of hip and pelvic disorders

“…Although L-PRP has been shown to contain the highest levels of growth factors and cytokines 27 , it induces catabolic effects and a significantly greater acute inflammatory response and thus may actually prolong the healing process 27-30 . Thus, the inclusion of white cells defeats the purpose of PRP. On the other hand, P-PRP induces mainly anabolic changes, and while this is generally a beneficial outcome, it could also result in scar tissue formation due to these anabolic effects 27,30 . Still, no randomized or prospective clinical studies have been performed to compare outcomes between leukocyte-rich versus leukocyte-poor PRP.…”