This 2014 study in the American Journal of Sports Medicine, led by Dr. Stacie Boswell during her research year in Dr. Lisa Fortier’s laboratory at Cornell University, tested how the makeup of platelet-rich plasma (PRP) affects healing in tendon tissue. Its practical conclusion — that reducing white blood cells matters more than maximizing platelets — has direct bearing on how PRP is prepared to treat tendon injuries in horses and people.
Increasing Platelet Concentrations in Leukocyte-Reduced Platelet-Rich Plasma Decrease Collagen Gene Synthesis in Tendons
Boswell SG, Schnabel LV, Mohammed HO, Sundman EA, Minas T, Fortier LA. American Journal of Sports Medicine. 2014 Jan;42(1):42-49.
Abstract
Background: Platelet-rich plasma (PRP) is used for the treatment of tendinopathy. There are numerous PRP preparations, and the optimal combination of platelets and leukocytes is not known.
Hypothesis: Within leukocyte-reduced PRP (lrPRP), there is a plateau effect of platelet concentration, with increasing platelet concentrations being detrimental to extracellular matrix synthesis.
Study design: Controlled laboratory study.
Methods: Different formulations of lrPRP with respect to the platelet:leukocyte ratio were generated from venous blood of 8 horses. Explants of the superficial digital flexor tendon were cultured in lrPRP products for 96 hours. Platelet-derived growth factor-BB (PDGF-BB), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), and interleukin-1β (IL-1β) concentrations were determined in the media by enzyme-linked immunosorbent assay. Gene expression in tendon tissue for collagen type I and III (COL1A1 and COL3A1), matrix metalloproteinase-3 and -13 (MMP-3 and MMP-13), cartilage oligomeric matrix protein (COMP), and IL-1β was determined.
Results: Complete blood counts verified leukocyte reduction and platelet enrichment in all PRP preparations. In the lrPRP preparation, the anabolic growth factors PDGF-BB and TGF-β1 were increased with increasing platelet concentrations, and the catabolic cytokine IL-1β was decreased with increasing platelet concentrations. Increasing the platelet concentration resulted in a significant reduction in COL1A1 and COL3A1 synthesis in tendons.
Conclusion: Increasing the platelet concentration within lrPRP preparations results in the delivery of more anabolic growth factors and less proinflammatory cytokines, but the biological effect on tendons is diminished metabolism as indicated by a decrease in the synthesis of both COL1A1 and COL3A1. Together, this information suggests that minimizing leukocytes in PRP is more important than maximizing platelet numbers with respect to decreasing inflammation and enhancing matrix gene synthesis.
Clinical relevance: This study suggests that reducing leukocytes to minimize catabolic signaling appears to be more important than increasing platelets in an effort to maximize anabolic signaling. Further, a maximum biological threshold of benefit was demonstrated with regard to the number of platelets beyond which further increases in platelet concentration did not result in further anabolic upregulation.
Read the full article at the publisher: doi.org/10.1177/0363546513507566. Citation on PubMed (PMID: 24136860).