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The potential use of allogeneic platelet-rich plasma for large bone defect treatment: Immunogenicity and defect healing efficacy

机译:异体富血小板血浆在大骨缺损治疗中的潜在用途:免疫原性和缺损愈合功效

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Autologous platelet-rich plasma (PRP) has been extensively investigated for large bone defect treatment, but its clinical application is harassed by controversial outcome, due to highly variable PRP quality among patients. Alternatively, allogeneic PRP from well-characterized donors cannot only generate more consistent and reliable therapeutic effect but also avoid harvesting large quantities of blood, an additional health burdens to patients. However, the use of allogeneic PRP for bone defect treatment is generally less investigated, especially for its immunogenicity in such application. Here, we meticulously investigated the immunogenicity of allogeneic PRP and evaluated its healing efficacy for critical-sized defect treatment. Allogeneic PRP contained 4.1-fold and 2.7- to 4.9-fold higher amount of platelets and growth factors than whole blood, respectively. The intramuscular injection of allogeneic PRP to rabbits did not trigger severe and chronic immunoresponse, evidenced by little change in muscular tissue microstructure and CD4+/CD8+ T lymphocyte subpopulation in peripheral blood. The implantation of allogeneic PRP/deproteinized bone matrix (DPB) constructs (PRP + DPB) successfully bridged 1.5-cm segmental radial defects in rabbits, achieving similar healing capacity as autologous MSC/DPB constructs (MSC + DPB), with greater bone formation (1.1-1.5??, p 0.05) and vascularization (1.3-1.6??, p 0.05) than DPB alone, shown by histomorphometric analysis, bone mineral density measurement, and radionuclide bone imaging. Furthermore, the implantation of both allogeneic PRP- and autologous MSC-mediated DPB constructs (PRP + MSC + DPB) resulted in the most robust bone regeneration (1.2-2.1??, p 0.05) and vascularization (1.3-2.0??, p 0.05) than others (PRP + DPB, MSC + DPB, or DPB alone). This study has demonstrated the promising use of allogeneic PRP for bone defect treatment with negligible immunogenicity, great healing efficacy, potentially more consistent quality, and no additional health burden to patients; additionally, the synergetic enhancing effect found between allogeneic PRP and autologous MSCs may shed a light on developing new therapeutic strategies for large bone defect treatment. ? 2013 Cognizant Comm. Corp.
机译:自体富血小板血浆(PRP)已被广泛研究用于大骨缺损的治疗,但由于患者之间PRP质量的高度差异,其临床应用受到争议性结果的困扰。或者,来自特征明确的供体的同种异体PRP不仅会产生更一致,更可靠的治疗效果,而且还避免收获大量血液,这给患者带来了额外的健康负担。但是,同种异体PRP在骨缺损治疗中的应用通常很少得到研究,尤其是在此类应用中具有免疫原性的情况。在这里,我们认真研究了同种异体PRP的免疫原性,并评估了其对关键尺寸缺陷治疗的治愈效果。同种异体PRP所含血小板和生长因子的量分别比全血高4.1倍和2.7至4.9倍。向兔子肌肉内注射同种异体PRP不会触发严重和慢性免疫反应,这通过外周血中肌肉组织微结构和CD4 + / CD8 + T淋巴细胞亚群的微小变化来证明。同种异体PRP /去蛋白骨基质(DPB)构建物(PRP + DPB)的植入成功弥合了兔的1.5厘米节段性radial骨缺损,达到了与自体MSC / DPB构建物(MSC + DPB)类似的愈合能力,并具有更大的骨形成(组织形态计量学分析,骨矿物质密度测量和放射性核素骨显像显示,单独使用DPB的血管生成率(1.1-1.5?,p <0.05)和血管化(1.3-1.6?,p <0.05)。此外,同种异体PRP和自体MSC介导的DPB结构(PRP + MSC + DPB)的植入导致最强健的骨再生(1.2-2.1?,p <0.05)和血管化(1.3-2.0 ?, p <0.05),而不是其他(PRP + DPB,MSC + DPB或单独的DPB)。这项研究表明,同种异体PRP可以用于免疫缺陷性,免疫原性可忽略不计,治愈效果更好,质量更稳定且对患者没有额外健康负担的骨缺损治疗。此外,同种异体PRP与自体MSC之间的协同增强作用可能为开发新的大骨缺损治疗策略提供了启示。 ? 2013 Cognizant Comm。公司

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