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Publications

Journal Article Review Epublish

PubMed: 40497973 DOI: 10.3390/cells14110797

The Potential of Red Blood Cells in Regenerative Medicine: A Paradigm Shift in Cellular Therapy.

Cells 14(11)

Authors: Fábio Ramos Costa, Joseph Purita, Ansar Mahmood, Rubens Martins, Bruno Costa, Bruno Lima Rodrigues, Stephany Cares Huber, Gabriel Silva Santos, Luyddy Pires, Gabriel Azzini, André Kruel, José Fábio Lana

Affiliations

  • Department of Orthopedics, FC Sports Traumatology, Salvador 40296-210, BA, Brazil.
  • Orthopedics, PUR-FORM, Boca Raton, FL 33432, USA.
  • Trauma and Orthopaedics Department, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham B15 2GW, UK.
  • Medical School, Tiradentes University Center, Maceió 57038-000, AL, Brazil.
  • Medical School, Zarns College, Salvador 41720-200, BA, Brazil.
  • Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil.
  • Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil.
  • Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil. Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil.
  • Department of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil. Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, SP, Brazil. Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, SP, Brazil. Clinical Research, Anna Vitória Lana Institute (IAVL), Indaiatuba 13334-170, SP, Brazil. Medical School, Jaguariúna University Center (UniFAJ), Jaguariúna 13911-094, SP, Brazil.

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.

MeSH

Cells, Extracellular Vesicles, Immunomodulation, Erythrocytes, Blood, Regenerative Medicine, Hemolysis, Tissue Engineering, Blood Cells, Therapeutics, Retention, Psychology