Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020
Abstract
:1. Introduction
2. The Rationale for Clinical Platelet-Rich Plasma Therapies
3. PRP Terminology and Classification
3.1. “Generic” PRP to Mimic the Onset of Healing
3.2. Confusing PRP Terminology and Synopsis of Proposed Classification Systems
3.3. PRP Preparation Methods Are a Work in Progress
3.4. The Current Status of PRP Classification Systems
4. Understanding In Vitro and In Vivo Platelet Dosing
The Significance of In Vitro Data on Platelet Concentrations
5. A Contemporary PRP Formulation: “Clinical PRP”
5.1. Clinical PRP Recipe
5.1.1. Platelet Granules
5.1.2. Platelet Concentration
5.1.3. Deleterious Red Blood Cells
5.1.4. Leukocytes in C-PRP
Neutrophils
Lymphocytes
Monocytes—Multipotential Repair Cells
5.2. Confusing Definitions for Leukocyte Fractions in PRP
6. Innate and Adaptive Immunomodulatory Capacities of PRP
6.1. Platelet Adhesion Molecules
6.2. Platelets and Leukocytes Play Pivotal Roles in Innate and Adaptive Immune Responses
6.2.1. Innate Immune System
Platelet-Leukocyte Interactions in Innate Immunity
6.2.2. Adaptive Immune System
Platelet-Leukocyte Interactions in Adaptive Immunity
6.3. Expanded Role of Platelet-Derived Serotonin in PRP
HT Paracrine and Autocrine Mechanisms
6.4. Immunomodulatory 5-HT Effects
7. PRP Analgesic Effects
8. PRP and Angiogenesis Effects
Pro- and Anti-Angiogenic Platelet Properties
9. Cell Senescence, Aging, and PRP
9.1. Effects of Aging and Cell Senescence
9.2. Cell Senescence and the Potential of PRP
10. The Role of Platelets in Bone Marrow Aspirate Concentrate
10.1. BMAC Repair Processes
10.2. Combining PRP and BMACs
10.3. PRP Growth Factors and BMAC Trophic Effects
11. Platelet Interactions with Anti-Platelet Medications and NSAIDs
12. Combining Platelet-Rich Plasma Applications with Rehabilitation
13. Future Prospect and Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
5-HT | serotonin |
5HTR | serotonin receptors |
Ang-1 | angiopoietin-1 |
BMA | bone marrow aspirate |
BMAC | bone marrow aspirate concentrate |
C-PRP | clinical platelet-rich plasma |
CD40L | cluster of differentiation 40 ligand |
CTCG | connective tissue growth factor |
CXCL | chemokine C-X-C motif ligand |
DC | dendritic cell |
EC | endothelial cells |
ECM | extracellular matrix |
EGF | epidermal growth factor |
EPC | endothelial progenitor cell |
FGF | fibroblast growth factor |
GP | glycoprotein |
HGF | hepatocyte growth factor |
IFN | interferon |
IGF | insulin-like growth factor |
IL | interleukin |
JAM | junctional adhesion molecule |
KGF | keratinocyte growth factor |
L-PRF | leucocyte platelet-rich plasma |
LP-PRP | leukocyte-poor platelet-rich plasma |
LR-PRP | leukocyte-rich platelet-rich plasma |
Mac-1 | macrophage-1 antigen |
MSC | mesenchymal stem cell |
MMP | matrix metalloproteinase |
MSK | musculoskeletal |
MΦ | macrophage |
NET | neutrophil extracellular trap |
NF-κB | nuclear factor kappa B |
NSAID | non-steroidal anti-inflammatory drug |
OA | osteoarthritis |
PPP | platelet-poor plasma |
P-PRF | pure platelet-rich fibrin |
P-PRP | pure platelet-rich plasma |
PDGF | platelet-derived growth factor |
PF4 | platelet factor 4 |
PFH | plasma-free hemoglobin |
PGF | platelet growth factor |
PPP | platelet-poor plasma |
PRP | platelet-rich plasma |
RANTES | regulated upon activation, normal T cell expressed and presumably secreted |
RBC | red blood cell |
SDF | stromal cell derived factor |
SDF-1α | stromal cell-derived factor 1 alpha |
SMC | smooth muscle cell |
TGF | transforming growth factor |
TLR | toll-like receptors |
TNF | tumor necrosis factor |
Treg | regular T lymphocyte |
VEGF | vascular endothelial growth factor |
vWF | von Willebrand factor |
WBC | white blood cells |
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PGF and Cytokines | Cell Sources | Function and Effects |
---|---|---|
PDGF (AA-BB-AB) | Platelets, endothelial cells, macrophages, smooth muscle cells | Mitogenic for mesenchymal cells and osteoblasts; stimulates chemotaxis and mitogenesis in fibroblast/ glial/smooth muscle cells; regulates collagenase secretion and collagen synthesis; stimulates macrophage and neutrophil chemotaxis |
TGF (α–β) | Macrophages, T lymphocytes, keratinocytes | Stimulates undifferentiated mesenchymal cell proliferation; regulates endothelial, fibroblastic, and osteoblastic mitogenesis; regulates collagen synthesis and collagenase secretion; regulates mitogenic effects of other growth factors; stimulates endothelial chemotaxis and angiogenesis; inhibits macrophage and lymphocyte proliferation |
VEGF | Platelets, macrophages, keratinocytes, endothelial cells | Increases angiogenesis and vessel permeability; stimulates mitogenesis for endothelial cells |
EGF | Platelets, macrophages, monocytes | Proliferation of keratinocytes, fibroblasts, stimulates mitogenesis for endothelial cells |
(a-b)-FGF | Platelets, macrophages, mesenchymal cells, chondrocytes, osteoblasts | Promotes growth and differentiation of chondrocytes and osteoblasts; mitogenic for mesenchymal cells, chondrocytes, and osteoblasts |
CTGF | Platelets, fibroblasts | Promotes angiogenesis, cartilage regeneration, fibrosis, and platelet adhesion |
IGF-1 | Platelets, plasma, epithelial cells, endothelial cells, fibroblasts, osteoblasts, bone matrix | Chemotactic for fibroblasts and stimulates protein synthesis. Enhances bone formation by proliferation and differentiation of osteoblasts |
HGF | Platelets, mesenchymal cells | Regulates cell growth and motility in epithelial/endothelial cells, supporting epithelial repair and neovascularization during wound healing |
KGF | Fibroblasts, mesenchymal cells | Regulates epithelial migration and proliferation |
Ang-1 | Platelets, neutrophils | Induces angiogenesis stimulating migration and proliferation of endothelial cells. Supports and stabilizes blood vessel development via the recruitment of pericyte |
PF4 | Platelets | Calls leucocytes and regulates their activation. Microbiocidal activities |
SDF-1α | Platelets, endothelial cells, fibroblasts | Calls CD34+ cells, induces their homing, proliferation and differentiation into endothelial progenitor cells stimulating angiogenesis. Calls mesenchymal stem cells and leucocytes |
TNF | Macrophages, mast cells, T lymphocytes | Regulates monocyte migration, fibroblast proliferation, macrophage activation, angiogenesis |
A-PRF | Advanced Platelet-Rich Fibrin |
ACP | Autologous Conditioned Plasma |
AGF | Autologous Growth Factors |
APG | Autologous Platelet Gel |
C-PRP | Clinical Platelet-Rich Plasma |
i-PRF | Injectable Platelet-Rich Fibrin |
LP-PRP | Leukocyte-Poor Platelet-Rich Plasma |
LR-PRP | Leukocyte-Rich Platelet-Rich Plasma |
PFC | Platelet-derived Factor Concentrate |
P-PRP | Pure Platelet Rich Plasma |
PFS | Platelet Fibrin Sealant |
PLG | Platelet-Leukocyte Gel |
PRF | Platelet-Rich Fibrin |
PRFM | Platelet-Rich Fibrin Matrix |
PRGF | Preparation Rich in Growth Factors |
Parameters | Differentials | Options |
---|---|---|
Biological Product Allocation | Autologous Allogeneic | Buffy Coat Partial Buffy Coat Fresh Frozen/Thawed Platelet Lysate Umbilical cord blood |
Preparation Technology | Gravitational Centrifugation Blood Salvage Blood Separators Plasmapheresis | Preparation time Spin-Cycles G-Forces |
Anticoagulation | ACD-A EDTA SC Heparin | |
Platelet dosing | Concentration ranges | 0–500 × 106/mL 500–1000 × 106/mL 1000–1500 × 106/mL >1500 × 106/mL |
Leukocytes Presence | Yes No | Neutrophils–Monocytes–Lymphocytes Poor–Poor |
RBC | Yes No | Hematocrit (range) |
Delivery Form | Liquid Coagulated | Partial Full |
Fibrin Matrix | Yes No | Concentration levels Content specific |
Activation | Yes No | CaCl Thrombin Collagen Electrical Freeze Sonication Light |
Additives | Biodegradable Scaffolds Matrices Autologous Biologics Non-autologous | Dexamethasone—HA—cPPP—BMAC—Adipose—Bone-Exosomes—Amniotic -Wharton Jelly—A-Cell Protein Preparations— Antibiotics—Pain medication |
Administration Routes | Topical IV Tissue structure Intraosseous | Soft tissue: Tendon—Ligament—Muscle—Scar Intradiscal—Epidural—Intrathecal—Intra-Articular |
Pro-Angiogenetic | Anti-Angiogenetic |
---|---|
VEGF | TGF-β1 |
PDGF | PAI |
TGF-β1 | TSP |
EGF | Angiostatin |
Serotonin | Endostatin |
SDF-1 | PF4 |
Angiopoietin -1, -2 | CXCL4L |
MMP -1, -2 | TIMPS |
IL-8 |
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Everts, P.; Onishi, K.; Jayaram, P.; Lana, J.F.; Mautner, K. Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020. Int. J. Mol. Sci. 2020, 21, 7794. https://doi.org/10.3390/ijms21207794
Everts P, Onishi K, Jayaram P, Lana JF, Mautner K. Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020. International Journal of Molecular Sciences. 2020; 21(20):7794. https://doi.org/10.3390/ijms21207794
Chicago/Turabian StyleEverts, Peter, Kentaro Onishi, Prathap Jayaram, José Fábio Lana, and Kenneth Mautner. 2020. "Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020" International Journal of Molecular Sciences 21, no. 20: 7794. https://doi.org/10.3390/ijms21207794