Bioventus, Durham, NC, USA.
Cornell University, Ithaca, NY, USA.
Cartilage. 2023 Dec;14(4):467-472. doi: 10.1177/19476035231159748. Epub 2023 Mar 13.
This study was conducted to compare therapeutically relevant properties of platelet-rich plasma (PRP), a commonly used autologous intra-articular treatment for osteoarthritis (OA), with those of a novel placental tissue particulate, PTP-001, which is in development as a regulated biologic treatment for knee OA.
Quantitative immunoassays were performed to determine the content of key growth/regulatory biofactors in PTP-001, and in leukocyte-rich (LR)-PRP or leukocyte-poor (LP)-PRP. An anti-inflammatory bioassay was used to evaluate the effects of each treatment on pro-inflammatory cytokine (tumor necrosis factor (TNF)-α) production in a macrophage cell culture system. Gene expression experiments were conducted using a co-culture system of human synoviocytes (pre-stimulated with interleukin (IL)-1β) and articular chondrocytes, with quantitative polymerase chain reaction analyses of the separate cellular compartments.
The concentrations of several biofactors (e.g., basic fibroblast growth factor, tissue inhibitor of metalloproteases-3, interleukin-1 receptor antagonist) representative of diverse disease-relevant mechanisms of action were significantly higher for PTP-001 relative to LR-PRP or LP-PRP. PTP-001 and PRP preparations were able to reduce TNF-α production in macrophage cell cultures; however, greater variability was observed for PRP in comparison with PTP-001. In the chondrocyte/synoviocyte co-culture experiments, PTP-001 and LR-PRP (but not LP-PRP) significantly reduced chondrocyte expression in cultures containing IL-1-pretreated synoviocytes. In addition, expression was reduced in the chondrocyte compartment following treatment with PTP-001 relative to PRP.
These findings support evidence of a potent, multifactorial mechanism of action for a consistently manufactured biologic (PTP-001), which may be of greater therapeutic benefit in comparison with more heterogeneous preparations of PRP which may be generated at the time of treatment.
本研究旨在比较富血小板血浆(PRP)与新型胎盘组织颗粒(PTP-001)的治疗相关特性,PRP 是一种常用于治疗骨关节炎(OA)的自体关节内治疗方法,而 PTP-001 是一种正在开发的用于治疗膝骨关节炎的调控生物治疗方法。
采用定量免疫分析法测定 PTP-001 及富含白细胞(LR)-PRP 或白细胞缺乏(LP)-PRP 中的关键生长/调节生物因子含量。采用抗炎生物测定法评估每种治疗方法对巨噬细胞培养系统中促炎细胞因子(肿瘤坏死因子(TNF)-α)产生的影响。采用人滑膜细胞(经白细胞介素(IL)-1β预刺激)和关节软骨细胞共培养系统进行基因表达实验,并用定量聚合酶链反应分析各细胞室的基因表达。
PTP-001 的几种生物因子(如碱性成纤维细胞生长因子、金属蛋白酶组织抑制剂-3、白细胞介素-1 受体拮抗剂)浓度明显高于 LR-PRP 或 LP-PRP,这些生物因子代表了多种与疾病相关的作用机制。PTP-001 和 PRP 制剂均能降低巨噬细胞培养物中 TNF-α的产生,但与 PTP-001 相比,PRP 制剂的变异性更大。在软骨细胞/滑膜细胞共培养实验中,PTP-001 和 LR-PRP(而非 LP-PRP)显著降低了含有 IL-1 预处理滑膜细胞的培养物中软骨细胞的表达。此外,与 PRP 相比,PTP-001 处理后软骨细胞室中的 表达也降低了。
这些发现支持了一种始终如一的制造生物制剂(PTP-001)具有强大的多因素作用机制的证据,与更具异质性的 PRP 制剂相比,它可能具有更大的治疗益处,PRP 制剂可能是在治疗时产生的。