Dr. Anas Makhzoum was the recipient of a 2019 ORADE Grant.
I would like to thank the ORA for allowing me the opportunity to attend the 10th annual TOBI conference in Chicago. The three-day long conference was packed with lectures discussing different topics in the world of regenerative medicine, and in particular, platelet-rich plasma (PRP).
Over the last few years, there has been a lot of hype around the use of PRP, and stem cells for treatment of various conditions despite lack of robust evidence for many of their applications.
The orthobiologics annual meeting (TOBI) provided me with a valuable opportunity to understand the hypothesis behind PRP and stem cell application and the evidence behind it for treatment of MSK disorders.
The meeting was well attended by a number of interested physicians and scientists in various specialties mainly physical medicine and rehab, sports medicine, orthopedic surgeons and a few rheumatologists. It was mostly focused on PRP applications, new protocol, and recent studies. Few sessions were dedicated to bone marrow aspirate concentrate BMAC and adipose tissue aspirate application.
Basic science:
The term “regenerative medicine” was first coined in 2011. However, the effect of various cytokines and growth factors in cartilage and soft tissues metabolism has been a topic of high importance since the 1980s.
Dr. Michael Fredericson, professor of PM&R at Stanford University, discussed in his lecture the effect of various cytokines on tissue regeneration.
Growth factors such as transforming growth factor TGF- B, insulin-like growth factor (IGF-1), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), all play a role in tissue regeneration and enhancing mesenchymal differentiation to generate other cells from the same embryonic origin. [i] [ii]
Stimulating undifferentiated mesenchymal can be of help in the treatment of a number of MSK complaints such as acute muscle/tendon/ligament injuries, chronic tendonosis, surgical repairs (hip labrum, rotator cuff, ACL and bone graft) and osteoarthritis.[iii]
Protocols:
PRP can either be leukocyte poor OR leukocyte rich PRP. Leukocyte rich PRP is better for acute injuries and should be avoided in knees osteoarthritis as it may lead to worse inflammatory reaction post injection. On the other hand, Leukocyte poor PRP is generally considered better for knee osteoarthritis application. [iv]
Harvested platelets concentration varies based on a number of factors including patient’s age, gender, associated diseases, hormonal disorders, blood dyscrasias, anti-inflammatory medication, and antibiotics [v]. For example, Naproxen use diminishes biological factor in LR-PRP [vi] . A one week Naproxen washout period is sufficient for recovery of PDGF-AA PFGF- AB and IL-6.
Dr. Guillermo Alvarez reviewed some of the early studies which showed some promising data in animal models treated with PRP. Previous trials on animal models showed orthoscopic and microscopic improvement of knee OA with PRP and bone marrow concentrate [vii] .
The routine use of PRP is an area of much debate. While there is some basic science evidence that supports the role of different cytokine in the repairing and remodeling of different damaged tissues (including acute and chronic tendinopathies and osteoarthritis), there is a scarcity of robust evidence to recommend the routine use of PRP for treatment of the above conditions, mostly due to variation in the PRP preparation method and protocols.
PRP in Osteoarthritis:
Although clinical data does not support cartilage regeneration in humans following PRP treatment until now, knee osteoarthritis subjective pain scores showed improvement in a number of studies presented during the meeting.
The significant improvement of pain and function parameters was thought to be due to possible better control of underlying inflammatory process of the knee rather than trophic effect of PRP on cartilage. [viii] .
Dr. Brian Cole, professor in the department of orthopedics at Rush University, presented a recent RCT result comparing PRP with hyaluronic acid for knee OA. He presented data suggesting better IKDA and VAS scores in the PRP group compared to Hylaoronic acid. No difference was found in WOMAC scores. [ix].
PRP and gluteal tendinopathy:
Dr. Jane Fitzpatric presented data from a recently published RCT in the American Journal of Sport medicine. The study concluded that a single intratendinous LR-PRP injection performed under ultrasound guidance resulted in greater improvement in pain and function than a single corticosteroid injection(CSI) in patients with chronic gluteal tendinopathy. The improvement after LR-PRP injection is sustained at 2 years, whereas the improvement from a CSI is maximal at 6 weeks and not maintained beyond 24 weeks.[x]
Although no safety and adverse effects signals related to administration of PRP have been reported so far, the debate continued during the meeting regarding the ultimate preparation method and frequency of administration. There is a great need for ongoing research on both basic science and clinical levels.
[i] Anitua E, Andia I, Sanchez M, et al. Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF productions by human tendon cells in culture. J Orthop Res 2005;23:281–286.
[ii] Tate KS, Crane DM. Platelet rich plasma grafts in musculoskeletal medicine. J Prolother 2010;2(2):371–376.
[iii] Ahmed, M. and Panagos, A. (2014) Intra-Articular Autologous Platelet-Rich Plasma Hip Injection May Result in Osteogenesis Depicted as an Increase in Femoral Neck Bone Density. Open Journal of Regenerative Medicine, 3, 39-42.
[iv] (Zhou, Y., Zhang, J., Wu, H., Hogan, M. and Wang, J. (2019). The differential effects of leukocyte-containing and pure platelet-rich plasma (PRP) on tendon stem/progenitor cells – implications of PRP application for the clinical treatment of tendon injuries.
[v] Mei-Dan O, Mann G, Maffulli N. Platelet-rich plasma: any substance into it? Br J Sports Med 2010;44(9):618–619.
[vi] Taniguchi, Y., Yoshioka, T., Sugaya, H., Gosho, M., Aoto, K., Kanamori, A. and Yamazaki, M. (2019). Growth factor levels in leukocyte-poor platelet-rich plasma and correlations with donor age, gender, and platelets in the Japanese population.
[vii] Bahmanpour S PhD, e. (2019). Effects of Platelet-Rich Plasma & Platelet-Rich Fibrin with and without Stromal Cell-Derived Factor-1 on Repairing Full-Thickness Cartilage Defects… – PubMed – NCBI. [online] Ncbi.nlm.nih.gov. Available at: https://www.ncbi.nlm.nih.gov/pubmed/?term=microscopic+and+histrologica+score+PRP+rabbits) [Accessed 23 Jun. 2019].
[viii] Buendía-López, D., Medina-Quirós, M. and Fernández-Villacañas Marín, M. (2019). Clinical and radiographic comparison of a single LP-PRP injection, a single hyaluronic acid injection and daily NSAID administration with a 52-week follow-up: a randomized controlled trial.
[ix] Cole BJ, e. (2019). Hyaluronic Acid Versus Platelet-Rich Plasma: A Prospective, Double-Blind Randomized Controlled Trial Comparing Clinical Outcomes and Effects on Int… – PubMed – NCBI. [online] Ncbi.nlm.nih.gov. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28146403 [Accessed 23 Jun. 2019].
[x] Fitzpatrick J, e. (2019). Leucocyte-Rich Platelet-Rich Plasma Treatment of Gluteus Medius and Minimus Tendinopathy: A Double-Blind Randomized Controlled Trial With 2-Year Fo… – PubMed – NCBI. [online] Ncbi.nlm.nih.gov. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30840831 [Accessed 23 Jun. 2019].
