Preparing PRP: More Questions than Answers

This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson. 

The use of platelet-rich plasma (PRP) in the treatment of tendinitis, some sports injuries, and osteoarthritis has been popularized over the past decade. Because there is “minimal” manipulation of biologic products such as PRP, their preparation is not subject to the rigid standards used for the development of pharmacologic products.

In a recent study of autologous PRP, investigators hypothesized that “lower levels of inflammatory cytokines (ICs) within PRP stimulate positive chondrocyte and macrophage responses irrespective of the age and OA disease state of the PRP donor”¹. To test this hypothesis, investigators made PRP preparations from young healthy individuals and older patients with end-stage OA using a modified double-spin protocol. The level of inflammatory cytokines (ICs) was identified in all PRP preparations. Chondrocytes were isolated from normal-appearing cartilage harvested from an arthritic knee during total joint arthroplasty. Alginate beads were created for culture and were treated with 10% PRP on days 0 and 2 of a 4-day culture period.

The results contradicted the hypothesis. There were a number of adverse results in the cultures treated with PRP donated by the OA group. Macrophage activation increased with OA disease status/age of the PRP donor. PRP from OA subjects significantly upregulated TNF-α (p <0.001) and MMP-9 (p<0.0001) in macrophage cultures irrespective of whether the PRP had “high” or “low” IC levels. Additionally, PRP from donors with OA decreased Col2a1 (p<0.05) and SOX9 (p<0.05) expression more than PRP from healthy donors, irrespective of IC grouping.

According to these findings, the functional effects of PRP appear to be dependent on the age and disease status of the plasma donor, as opposed to the IC concentration. This suggests that a more complex interaction with age or OA-related molecular factors might dictate the effect of PRP.

In a separate study, the issue of variation of PRP preparations in research was evaluated by Delphi consensus and other methodologies.² One key consensus of the PRP experts was the importance of detailing the cellular composition of whole blood and the delivered PRP. The experts also noted marked individual variation in PRP and the need for a clear understanding of the factors influencing such variation.

References

1. O’Donnell C, Migliore E, Grandi FC, Lingampalli N, Raghu H, Giori N N, J, Indelli PF, Robinson WH, Bhutani N, Chu CR. Donor Specific Effects of Platelet-Rich Plasma for the Treatment of Osteoarthritis Trans Orthop Res Sco. 2018. Paper 0063
2. Murray IR, Geeslin AG, Goudie EB, Petrigliano FA, LaPrade RF. Minimum Information for Studies Evaluating Biologics in Orthopaedics (MIBO): Platelet-Rich Plasma and Mesenchymal Stem Cells. J Bone Joint Surg Am. 2017 May 17;99(10):809-819. doi: 10.2106/JBJS.16.00793