Efficacy of autologous leukocyte-reduced platelet-rich plasma therapy for patellar tendinopathy in a rat treadmill model

Abstract

SummaryBackground: An autologous platelet-rich plasma (PRP) therapy has currently been applied for the tendinopathy; however, its efficacy and an optimal platelets concentration in PRP were uncertain. We analyzed them in an animal model prepared using a repetitive running exercise. Methods: We made the tendinopathy rat model of patellar tendon using a rodent treadmill machine. Rats with tendinopathy were injected with leukocyte-reduced PRP at the platelets concentration of 1.0×10 6 /µL (P10 group), PRP at the platelets concentration of 5.0×10 5 /µL (P5 group) or normal saline (control group) into the space between the patellar tendon and the fat pad bilaterally or were multiply dry-needled at the tibial insertion site (MN group) at once. To assess the pain-reliving effect, the spontaneous locomotor activities at night (12 h) were measured every day. Histological sections of the patellar tendon stained with hematoxylineosin or prepared by TdT-mediated dUTP nick end labeling were microscopically analyzed. Results: The numbers of spontaneous locomotor activities in the P10 group were significantly larger than those in the P5, MN or control groups and they recovered up to a healthy level. On histologic examinations, the numbers of microtears, laminations, or apoptotic cells in the patellar tendons in the P10 or P5 groups were significantly lower than those in the MN or control groups, although no significant differences were observed between the P10 and P5 groups. Conclusions:The injections of an autologous leukocyte-reduced PRP were effective for pain relief and for partial restoration of the patellar tendon in the tendinopathy rat model. The injections of a PRP at the platelets concentration of 1.0×10 6 /µL completely relieved the pain and were more effective than those at the platelets concentration of 5.0×10 5 /µL whereas there was no difference for the effect of histological restoration or apoptosis inhibition between them.

Effect of leukocyte-reduced platelet-rich plasma on osteoarthritis caused by cranial cruciate ligament rupture: A canine gait analysis model

“…Recent reports have shown that the presence of leukocytes in PRP preparations may be detrimental to healing, due to their involvement in the inflammatory response [ 27 ] causing loss of pain relief efficacy [ 28 ]. We avoided this complication, because our PRP was prepared with nearly complete absence of leukocytes.…”

Optimized platelet rich plasma releasate (O-rPRP) repairs galactosemia-induced ovarian follicular loss in rats by activating mTOR signaling and inhibiting apoptosis

“…To determine which dose of O-rPRP was more protective against toxic galactose, two doses of rPRP (0.25 and 0.5 ml/kg) [ 30 , 31 ] were tested. Upon administration, rPRP was diluted with PBS at 1:3 (0.25 and 0.5 ml/kg rPRP were added into 0.5 and 1 ml of PBS respectively) and mixed thoroughly.…”

Variables affecting the potential efficacy of PRP in providing chronic pain relief

“…However, other clinical studies found that PRP reduces or eliminates pain, such as that associated with tendinosis,9–11 rotator cuff tears,12,13 osteoarthritis,14 plantar fasciitis,15 and muscle injuries 16. PRP is also reported to act as an analgesic in animal pain models, such as rat tendinosis,17 rotator cuff injury,18 and dog tendon injury 19. In general, the findings of PRP analgesic influence led to the conclusion that although there are suggestions that PRP can act as an analgesic, the variability in study outcomes resulted from their small study sample sizes and the inclusion of too many variables, which did not allow the studies to be compared, or that the comparative analyses of the outcomes of different studies do not provide sufficient statistical support for the conclusion that PRP acts as an analgesic 4…”

“…One clinical study reported that PRP with a platelet concentration of 4- to 5-fold above average baseline count (varying from 1.5 and 3×10 5 /μL) enhanced peri-implant bone regeneration, while both lower and higher concentrations had inhibitory effects 59. A study on the rat tendinopathy model found that PRP with a platelet concentration of 1.0×10 6 / μ L induced complete pain relief, whereas PRP with half the platelet concentration induced significantly less pain relief 17. However, knowing what concentration of platelets in PRP induces the maximum analgesic effect requires understanding more than just the PRP platelet concentration.…”

“…PRP leukocyte count is dependent on the PRP separation device with leukocyte concentrations varying from 0.13- to 5-fold over whole blood 20. Although the injection of L-PRP has been reported to be beneficial in reducing tendinopathy,71 PRP with a reduced leukocyte concentration has also been reported to increase the capacity of PRP to reduce pain 17. However, while the leukocyte concentration is influenced by the PRP preparation device, it is also influenced by leukocyte levels in whole blood, with predictors of significantly elevated leukocyte counts including young age, male sex, increased body mass index, smoking, and low alcohol consumption 72.…”