The Potential of red blood cells in regenerative medicine: a paradigm shift in cellular therapy
Costa, Fábio Ramos Purita, Joseph Mahmood, Ansar Martins, Rubens Costa, Bruno Rodrigues, Bruno Lima Huber, Stephany Cares Santos, Gabriel Silva Pires, Luyddy Azzini, Gabriel
Costa, Fábio Ramos
Purita, Joseph
Mahmood, Ansar
Martins, Rubens
Costa, Bruno
Rodrigues, Bruno Lima
Huber, Stephany Cares
Santos, Gabriel Silva
Pires, Luyddy
Azzini, Gabriel
Affiliation
FC Sports Traumatology; PUR-FORM; University Hospitals Birmingham NHS Foundation Trust; Tiradentes University Center; Zarns College; Brazilian Institute of Regenerative Medicine; Orthoregen International Course; Max Planck University Center; Anna Vitória Lana Institute; Jaguariúna University Center
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Publication date
2025-05-29
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Abstract
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.
Citation
Costa FR, Purita J, Mahmood A, Martins R, Costa B, Rodrigues BL, Huber SC, Santos GS, Pires L, Azzini G, Kruel A, Lana JF. The Potential of Red Blood Cells in Regenerative Medicine: A Paradigm Shift in Cellular Therapy. Cells. 2025 May 29;14(11):797. doi: 10.3390/cells14110797.
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Article