Platelet-Rich Plasma Stimulates Cell Proliferation and Enhances Matrix Gene Expression and Synthesis in Tenocytes From Human Rotator Cuff Tendons With Degenerative Tears.
Jo CH, Kim JE, Yoon KS, Shin S. Am J Sports Med. 2012 Feb 23. [Epub ahead of print]
Platelet-rich plasma (PRP) injections have been a very hot topic in sports medicine the past year and similarly SMR has several posts about the results of the research. The results of these studies have varying results depending on the tissue type (tendon, ligament, etc), location (shoulder, knee, etc), and injury onset (acute vs chronic). However, there has been a lack of controlled in vitro experiments on cells from injured tissue to determine the underlying mechanisms of PRP. Therefore, the purpose of the current study was to determine the effect of PRP on tendon cell (tenocytes) proliferation (increasing cell numbers), as well as protein formation and gene expression related to the tendon matrix (glycosaminoglycan [GAG] and total collagen). The cells were collected from degenerative human rotator cuff tendons. Jo et al. excised 3 x 3 mm pieces of torn rotator cuff tendons from 9 patients during arthroscopic rotator cuff repair surgery. The tissue was processed to release the tenocytes and isolate them in cell culture. The same patients had blood drawn and used to create PRP gels to be used in the cell culture of the tenocytes. The authors assessed 2 types of PRP preparations and one platelet-poor plasma control (PPP). The 2 PRP preparations were PRP activated with calcium (PRP-Ca) and PRP activated with calcium and thrombin (PRP-Ca-Thr). The PRP gels also had varying levels of platelet concentrations (100 up to 16,000 X 103 platelets/µL). The PRP was left in the cell culture for 7 and 14 days. After the period of exposure the tenocytes were examined for cell proliferation, matrix gene expression (major structural components of tendons: collagen I, III, scleraxis, decorin, and tenascin-C), and matrix protein formation (GAG and total collagen). They found at day 7 the PRP-Ca group at 4000 X 103 platelets/µL had the highest cell proliferation but it seemed to plateau at 2000 X 103 cells/µL. The PRP-Ca-Thr group had the highest cell proliferation at 8000 X 103 platelets/µL but it seemed to plateau at 400 X 103 cells/µL. The PPP didn’t increase cell proliferation compared to untreated cells. Similar results were found at 14 days. Both PRP conditions increased collagen I & III gene expression at day 7 and only increased collagen III at day 14. The PPP group did not show any changes. All three conditions had an increased expression of decorin at day 14. Tenascin-C gene expression was increased at day 7 and 14 by the PRP-Ca-Thr group but not the PPP or the PRP-Ca groups. Both PRP conditions had increased expression of scleraxis at day 14 but not in the PPP group. Total collagen content was increased by all three groups at days 7 and 14. Both PRP groups also increased GAG synthesis at day 14.
The results of this study demonstrated that PRP improved tenocyte proliferation, tendon matrix expression/synthesis of several important genes and proteins that are responsible for tendon growth and healing. This study is very interesting because it is one of the first investigations to study the effect of PRP on degenerative tendon in a very controlled cell culture experiment. Rotator cuff tears are notorious for failed healing, the mechanism is not completely understood. Since rotator cuff tears are typically a chronic injury and the healing process might need a jump start PRP would seem a likely candidate to aid in healing and reduce failures. Clinically these study findings suggests that PRP may create an optimal environment for rotator cuff healing. However, the petri dish is far from the in-vivo human rotator cuff. The in-vivo environment is much more complex with high tensile loads, tissue movement, and compression. This environment can create many challenges when attempting to obtain successful results like the current study. In addition, it is still unknown if the PRP injection remains at the injury site or quickly diffuses to the surrounding tissues or just gets absorbed by the body. All of these situations can occur and dramatically affect the results clinically. Much more research is needed to determine the optimal delivery method and ways to optimize the mechanical loading at the healing insertion site. Have you seen successful outcomes after PRP injections in rotator cuff tear patients?
Written by: Stephen Thomas
Jo CH, Kim JE, Yoon KS, & Shin S (2012). Platelet-Rich Plasma Stimulates Cell Proliferation and Enhances Matrix Gene Expression and Synthesis in Tenocytes From Human Rotator Cuff Tendons With Degenerative Tears. The American journal of sports medicine PMID: 22366517