Comparative evaluation of leukocyte- and platelet-rich plasma and pure platelet-rich plasma for cartilage regeneration

Zhengliang Xu,Yuelei Zhang,Changqing Zhang,Wenjing Yin,Xuetao Xie,Yixuan Chen,Xin Qi

doi:10.1038/srep43301

Abstract

Platelet-rich plasma (PRP) has gained growing popularity in the treatment of articular cartilage lesions in the last decade. However, the potential harmful effects of leukocytes in PRP on cartilage regeneration have seldom been studied in vitro, and not at all in vivo yet. The objective of the present study is to compare the effects of leukocyte- and platelet-rich plasma (L-PRP) and pure platelet-rich plasma (P-PRP) on cartilage repair and NF-κB pathway, in order to explore the mechanism underlying the function of leukocytes in PRP in cartilage regeneration. The constituent analysis showed that P-PRP had significantly lower concentrations of leukocytes and pro-inflammatory cytokines compared with L-PRP. In addition, cell proliferation and differentiation assays indicated P-PRP promoted growth and chondrogenesis of rabbit bone marrow mesenchymal stem cells (rBMSC) significantly compared with L-PRP. Despite similarity in macroscopic appearance, the implantation of P-PRP combining rBMSC in vivo yielded better cartilage repair results than the L-PRP group based on histological examination. Importantly, the therapeutic effects of PRP on cartilage regeneration could be enhanced by removing leukocytes to avoid the activation of the NF-κB pathway. Thus, PRP without concentrated leukocytes may be more suitable for the treatment of articular cartilage lesions.

Highlights

Study by Filardo[15], leukocyte-rich PRP (L-PRP) resulted in a higher incidence of side effects in the treatment of osteoarthritis compared with pure PRP (P-PRP), which had a lower leukocyte concentration, possibly due to the fact that leukocytes in PRP may deliver pro-inflammatory cytokines, such as interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α), at the site of injection, resulting in the production of destructive proteases that inhibit the formation and promote the degradation of extracellular matrix[15,16,17]
The findings showed that both L-PRP and P-PRP had ~6-fold platelet concentration and increased PDGF-AB and TGF-β1 concentrations compared with the whole blood
L-PRP induced the nuclear translocation of nuclear factor κB (NF-κB) p65, increased the messenger RNA (mRNA) expression of inducible nitric oxide synthase (iNOS) and COX-2, and enhanced the production of nitric oxide (NO) and Prostaglandin E2 (PGE2) in rabbit BMSC (rBMSC), Figure 5

Summary

Introduction

Study by Filardo[15], leukocyte-rich PRP (L-PRP) resulted in a higher incidence of side effects in the treatment of osteoarthritis compared with pure PRP (P-PRP), which had a lower leukocyte concentration, possibly due to the fact that leukocytes in PRP may deliver pro-inflammatory cytokines, such as interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α), at the site of injection, resulting in the production of destructive proteases that inhibit the formation and promote the degradation of extracellular matrix[15,16,17]. IL-1βand TNF-αinduce deleterious effects through the nuclear factor κB (NF-κB) signalling pathway[18,19]. The concentrated leukocytes in L-PRP may activate the NF-κB pathway through IL-1βand TNF-αto inhibit tissue healing. As a primary cell candidate for cartilage tissue engineering, BMSC has been extensively studied to repair osteochondral defects and enhance cartilage regeneration[22,23]. The objective of the present study was to compare the effects of L-PRP and P-PRP (PRPs) on rabbit BMSC (rBMSC) in vitro and on cartilage repair in vivo and preliminarily explore the mechanism to improve the efficacy of PRP therapy

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Conclusion