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

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,...

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Main 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
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/11/797
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author 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
author_facet 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
author_sort Fábio Ramos Costa
collection DOAJ
description 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.
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spelling doaj-art-a1a2c9e3a9044e1eb3ff2a06ba237b4c2025-08-20T03:11:30ZengMDPI AGCells2073-44092025-05-01141179710.3390/cells14110797The Potential of Red Blood Cells in Regenerative Medicine: A Paradigm Shift in Cellular TherapyFábio Ramos Costa0Joseph Purita1Ansar Mahmood2Rubens Martins3Bruno Costa4Bruno Lima Rodrigues5Stephany Cares Huber6Gabriel Silva Santos7Luyddy Pires8Gabriel Azzini9André Kruel10José Fábio Lana11Department of Orthopedics, FC Sports Traumatology, Salvador 40296-210, BA, BrazilOrthopedics, PUR-FORM, Boca Raton, FL 33432, USATrauma and Orthopaedics Department, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham B15 2GW, UKMedical School, Tiradentes University Center, Maceió 57038-000, AL, BrazilMedical School, Zarns College, Salvador 41720-200, BA, BrazilDepartment of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, BrazilDepartment of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, BrazilDepartment of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, BrazilDepartment of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, BrazilDepartment of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, BrazilDepartment of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, BrazilDepartment of Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, BrazilRed 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.https://www.mdpi.com/2073-4409/14/11/797red blood cellsregenerative medicineextracellular vesiclesimmunomodulationtissue engineering
spellingShingle 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
The Potential of Red Blood Cells in Regenerative Medicine: A Paradigm Shift in Cellular Therapy
Cells
red blood cells
regenerative medicine
extracellular vesicles
immunomodulation
tissue engineering
title The Potential of Red Blood Cells in Regenerative Medicine: A Paradigm Shift in Cellular Therapy
title_full The Potential of Red Blood Cells in Regenerative Medicine: A Paradigm Shift in Cellular Therapy
title_fullStr The Potential of Red Blood Cells in Regenerative Medicine: A Paradigm Shift in Cellular Therapy
title_full_unstemmed The Potential of Red Blood Cells in Regenerative Medicine: A Paradigm Shift in Cellular Therapy
title_short The Potential of Red Blood Cells in Regenerative Medicine: A Paradigm Shift in Cellular Therapy
title_sort potential of red blood cells in regenerative medicine a paradigm shift in cellular therapy
topic red blood cells
regenerative medicine
extracellular vesicles
immunomodulation
tissue engineering
url https://www.mdpi.com/2073-4409/14/11/797
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