Costa Fábio Ramos, Purita Joseph, Mahmood Ansar, Martins Rubens, Costa Bruno, Rodrigues Bruno Lima, Huber Stephany Cares, Santos Gabriel Silva, Pires Luyddy, Azzini Gabriel, Kruel André, Lana José Fábio
Department of Orthopedics, FC Sports Traumatology, Salvador 40296-210, BA, Brazil.
Orthopedics, PUR-FORM, Boca Raton, FL 33432, USA.
Cells. 2025 May 29;14(11):797. doi: 10.3390/cells14110797.
Red blood cells (RBCs) have traditionally been excluded from orthobiologic formulations due to inflammation, oxidative stress, and hemolysis concerns. However, emerging evidence suggests that RBCs may play an active role in regenerative medicine, contributing to immune modulation, vascular support, and oxidative balance. Their interactions with macrophages, involvement in nitric oxide signaling, and release of extracellular vesicles suggest they may influence tissue repair more than previously assumed. Despite these potential benefits, RBC retention in orthobiologic preparations like platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) remains controversial, with most protocols favoring their removal in the absence of robust translational clinical data. This review explores the biological functions of RBCs in regenerative medicine, their potential contributions to PRP and BMAC, and the challenges associated with their inclusion. While concerns about hemolysis and inflammation persist, controlled studies are needed to determine whether selective RBC retention could enhance musculoskeletal healing in some scenarios. Future research should focus on optimizing RBC processing techniques and evaluating their impact on clinical applications. Addressing these gaps will clarify whether RBCs represent an overlooked but valuable component in regenerative therapies or their exclusion remains justified.
由于炎症、氧化应激和溶血问题，红细胞（RBCs）传统上被排除在骨科生物制剂之外。然而，新出现的证据表明，红细胞可能在再生医学中发挥积极作用，有助于免疫调节、血管支持和氧化平衡。它们与巨噬细胞的相互作用、参与一氧化氮信号传导以及细胞外囊泡的释放表明，它们对组织修复的影响可能比以前认为的更大。尽管有这些潜在益处，但红细胞在富血小板血浆（PRP）和骨髓抽吸浓缩物（BMAC）等骨科生物制剂中的留存仍存在争议，在缺乏有力的转化临床数据的情况下，大多数方案倾向于将其去除。本综述探讨了红细胞在再生医学中的生物学功能、它们对PRP和BMAC的潜在贡献以及与它们纳入相关的挑战。虽然对溶血和炎症的担忧仍然存在，但需要进行对照研究，以确定在某些情况下选择性留存红细胞是否可以增强肌肉骨骼愈合。未来的研究应侧重于优化红细胞处理技术，并评估它们对临床应用的影响。填补这些空白将阐明红细胞是否是再生疗法中一个被忽视但有价值的组成部分，或者将它们排除是否仍然合理。
