Not All Platelets Are Created Equal: A Review on Platelet Aging and Functional Quality in Regenerative Medicine

Platelet-rich plasma (PRP) is widely used in regenerative medicine, yet clinical outcomes remain inconsistent. While traditional strategies have focused on platelet concentration and activation methods, emerging evidence suggests that the biological age of platelets, especially platelet senescence,...

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Main Authors: Fábio Ramos Costa, Joseph Purita, Rubens Martins, Bruno Costa, Lucas Villasboas de Oliveira, Stephany Cares Huber, Gabriel Silva Santos, Luyddy Pires, Gabriel Azzini, André Kruel, José Fábio Lana
Format: Article
Language:English
Published: MDPI AG 2025-08-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/15/1206
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author Fábio Ramos Costa
Joseph Purita
Rubens Martins
Bruno Costa
Lucas Villasboas de Oliveira
Stephany Cares Huber
Gabriel Silva Santos
Luyddy Pires
Gabriel Azzini
André Kruel
José Fábio Lana
author_facet Fábio Ramos Costa
Joseph Purita
Rubens Martins
Bruno Costa
Lucas Villasboas de Oliveira
Stephany Cares Huber
Gabriel Silva Santos
Luyddy Pires
Gabriel Azzini
André Kruel
José Fábio Lana
author_sort Fábio Ramos Costa
collection DOAJ
description Platelet-rich plasma (PRP) is widely used in regenerative medicine, yet clinical outcomes remain inconsistent. While traditional strategies have focused on platelet concentration and activation methods, emerging evidence suggests that the biological age of platelets, especially platelet senescence, may be a critical but overlooked factor influencing therapeutic efficacy. Senescent platelets display reduced granule content, impaired responsiveness, and heightened pro-inflammatory behavior, all of which can compromise tissue repair and regeneration. This review explores the mechanisms underlying platelet aging, including oxidative stress, mitochondrial dysfunction, and systemic inflammation, and examines how these factors influence PRP performance across diverse clinical contexts. We discuss the functional consequences of platelet senescence, the impact of comorbidities and aging on PRP quality, and current tools to assess platelet functionality, such as HLA-I–based flow cytometry. In addition, we present strategies for pre-procedural optimization, advanced processing techniques, and adjunctive therapies aimed at enhancing platelet quality. Finally, we challenge the prevailing emphasis on high-volume blood collection, highlighting the limitations of quantity-focused protocols and advocating for a shift toward biologically precise, function-driven regenerative interventions. Recognizing and addressing platelet senescence is a key step toward unlocking the full therapeutic potential of PRP-based interventions.
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spelling doaj-art-3669b18e78694f3889a602f9b3b37b262025-08-20T04:00:54ZengMDPI AGCells2073-44092025-08-011415120610.3390/cells14151206Not All Platelets Are Created Equal: A Review on Platelet Aging and Functional Quality in Regenerative MedicineFábio Ramos Costa0Joseph Purita1Rubens Martins2Bruno Costa3Lucas Villasboas de Oliveira4Stephany Cares Huber5Gabriel Silva Santos6Luyddy Pires7Gabriel Azzini8André Kruel9José Fábio Lana10Department of Orthopedics, FC Sports Traumatology, Salvador 40296-210, BA, BrazilPUR-FORM, Boca Raton, FL 33432, USAMedical School, Tiradentes University Center, Maceió 57038-000, AL, BrazilMedical School, Zarns College, Salvador 41720-200, BA, BrazilDepartment of Internal Medicine, Hospital Geral Roberto Santos, Salvador 40301-110, 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, BrazilPlatelet-rich plasma (PRP) is widely used in regenerative medicine, yet clinical outcomes remain inconsistent. While traditional strategies have focused on platelet concentration and activation methods, emerging evidence suggests that the biological age of platelets, especially platelet senescence, may be a critical but overlooked factor influencing therapeutic efficacy. Senescent platelets display reduced granule content, impaired responsiveness, and heightened pro-inflammatory behavior, all of which can compromise tissue repair and regeneration. This review explores the mechanisms underlying platelet aging, including oxidative stress, mitochondrial dysfunction, and systemic inflammation, and examines how these factors influence PRP performance across diverse clinical contexts. We discuss the functional consequences of platelet senescence, the impact of comorbidities and aging on PRP quality, and current tools to assess platelet functionality, such as HLA-I–based flow cytometry. In addition, we present strategies for pre-procedural optimization, advanced processing techniques, and adjunctive therapies aimed at enhancing platelet quality. Finally, we challenge the prevailing emphasis on high-volume blood collection, highlighting the limitations of quantity-focused protocols and advocating for a shift toward biologically precise, function-driven regenerative interventions. Recognizing and addressing platelet senescence is a key step toward unlocking the full therapeutic potential of PRP-based interventions.https://www.mdpi.com/2073-4409/14/15/1206platelet senescenceplatelet-rich plasmaregenerative medicineoxidative stressplatelet biomarkers
spellingShingle Fábio Ramos Costa
Joseph Purita
Rubens Martins
Bruno Costa
Lucas Villasboas de Oliveira
Stephany Cares Huber
Gabriel Silva Santos
Luyddy Pires
Gabriel Azzini
André Kruel
José Fábio Lana
Not All Platelets Are Created Equal: A Review on Platelet Aging and Functional Quality in Regenerative Medicine
Cells
platelet senescence
platelet-rich plasma
regenerative medicine
oxidative stress
platelet biomarkers
title Not All Platelets Are Created Equal: A Review on Platelet Aging and Functional Quality in Regenerative Medicine
title_full Not All Platelets Are Created Equal: A Review on Platelet Aging and Functional Quality in Regenerative Medicine
title_fullStr Not All Platelets Are Created Equal: A Review on Platelet Aging and Functional Quality in Regenerative Medicine
title_full_unstemmed Not All Platelets Are Created Equal: A Review on Platelet Aging and Functional Quality in Regenerative Medicine
title_short Not All Platelets Are Created Equal: A Review on Platelet Aging and Functional Quality in Regenerative Medicine
title_sort not all platelets are created equal a review on platelet aging and functional quality in regenerative medicine
topic platelet senescence
platelet-rich plasma
regenerative medicine
oxidative stress
platelet biomarkers
url https://www.mdpi.com/2073-4409/14/15/1206
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