I. Introduction A FUNCTIONAL relationship between cell growth and the initiation and progression of events associated with differentiation has been a fundamental question challenging developmental biologists for more than a century. In the case of bone, as observed with other cells and tissue, the relationship of growth and differentiation must be maintained and stringently regulated, both during development and throughout the life of the organism, to support tissue remodeling. For many years, bone was defined anatomically and examined largely in a descriptive manner by ultrastructural analysis and by biochemical and histochemical methods. These studies provided the basis for our understanding of bone tissue organization and orchestration of the progressive recruitment, proliferation, and differentiation of the various cellular components of bone tissue. Now, complemented by an increased knowledge of molecular mechanisms that are associated with and regulate expression of genes encoding phenotypic compone...

Molecular mechanism mediating proliferation, defferentiation interralationships during progressie development of the osteoblast phenotype

Platelet concentrates (PCs), mostly represented by platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) are autologous biological blood-derived products that may combine plasma/platelet-derived bioactive components, together with fibrin-forming protein able to create a natural three-dimensional scaffold. These types of products are safely used in clinical applications due to the autologous-derived source and the minimally invasive application procedure. In this narrative review, we focus on three main topics concerning the use of platelet concentrate for treating musculoskeletal conditions: (a) the different procedures to prepare PCs, (b) the composition of PCs that is related to the type of methodological procedure adopted and (c) the clinical application in musculoskeletal medicine, efficacy and main limits of the different studies.

Platelet Concentrates in Musculoskeletal Medicine

There is good scientific rationale to support the use of growth factors to promote musculoskeletal tissue regeneration. However, the clinical effectiveness of platelet-rich plasma (PRP) and other blood-derived products has yet to be proven. Characterization and reporting of PRP preparation protocols utilized in clinical trials for the treatment of musculoskeletal disease is highly inconsistent, and the majority of studies do not provide sufficient information to allow the protocols to be reproduced. Furthermore, the reporting of blood-derived products in orthopaedics is limited by the multiple PRP classification systems available, which makes comparison of results between studies challenging. Several attempts have been made to characterize and classify PRP; however, no consensus has been reached, and there is lack of a comprehensive and validated classification. In this annotation, we outline existing systems used to classify preparations of PRP, highlighting their advantages and limitations. There remains a need for standardized universal nomenclature to describe biological therapies, as well as a comprehensive and reproducible classification system for autologous blood-derived products. Cite this article: Bone Joint J 2019;101-B:891-896.

Classification systems for platelet-rich plasma

According to the World Health organization (WHO), more than 10% in people older than 60 years suffer from osteoarthritis (OA). Over the last years, there has been an increased interest around regenerative medicine, especially regarding stem cell treatments and related applications. We hypothesize that stem cell therapies can represent a feasible option for idiopathic knee OA, delaying or even avoiding the joint replacement. To emphasize the potential of percutaneous injections of mesenchymal stem cells for knee OA, a comprehensive systematic review of the literature was conducted. Two independent authors (FM, GC) performed the literature search. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). The main databases were accessed: Pubmed, Embase, Google Scholar, Cochrane Systematic Reviews, Scopus, AMED. For this systematic review, all articles treating percutaneous injections of mesenchymal stem cells for knee OA were considered. Because of the rapid advancements promoted by the scientific progress on stem cell expansion and processing, only articles published within the last five years were included. Solely articles reporting the outcomes of interest across 6- and 12-month follow-up were recruited for eligibility. We included only studies reporting quantitative data under the outcomes of interest. We referred for the quality assessment to the Coleman Methodology Score (CMS). The statistical analysis was performed with Review Manager Software 5.3 (The Nordic Cochrane Centre, Copenhagen). A total of 18 studies were enrolled in the present study, comprising 1069 treated knees. The mean age of the samples was 57.39 ± 7.37 years. 72% of the included studies harvested the stem cells from the iliac crest (bone marrow-derived MSCs), the remaining 28% from the adipose tissue (adipose-derived MSCs). The mean visual analogic scale improved from 18.37 to 30.98 and 36.91 at 6- and 12-month follow-up, respectively. The mean WOMAC score improved from 25.66 to 25.23 and 15.60 at 6- and 12-month follow-up, respectively. The mean walking distance improved from 71.90 to 152.22 and 316.72 at 6- and 12-month follow-up, respectively. The mean Lequesne scale improved from 33.76 to 12.90 at 12-month follow-up. The KOOS score improved from 41.07 to 8.47% and 18.94 at 6- and 12-month follow-up. All the KOOS subscales improved significantly from the baseline. A total of 136 (12.7%) local complications were detected. According to the current evidences and the main findings of this systematic review, we reported that MSC infiltrations for knee OA can represent a feasible option, leading to an overall remarkable improvement of all clinical and functional considered outcomes, regardless of the cell source. Patients treated at earlier-degeneration stages reported statistically significant greater outcomes. The pain and function scores were improved considerably, thus, leading to a significant improvement of patient participation in recreational activities and quality of life.

https://link.springer.com/content/pdf/10.1007/s00402-019-03267-8.pdf

Improved outcomes after mesenchymal stem cells injections for knee osteoarthritis: results at 12-months follow-up: a systematic review of the literature.

Purpose To perform a randomized controlled trial comparing platelet-rich plasma (PRP) with standard corticosteroid (CS) injection in providing pain relief and improved function in patients with rotator cuff tendinopathy and partial-thickness rotator cuff tears (PTRCTs). Methods This double-blind randomized controlled trial enrolled patients with ultrasound-proven or magnetic resonance imaging–proven PTRCTs who received either an ultrasound-guided PRP or CS injection. Patients completed patient-reported outcome assessments at baseline and at 6 weeks, 3 months, and 12 months after injection. The primary outcome was improvement in the visual analog scale (VAS) score for pain. Secondary outcomes included changes in American Shoulder and Elbow Surgeons (ASES) and Western Ontario Rotator Cuff Index (WORC) scores. Treatment failure was defined as subsequent injection, consent to undergo surgery, or operative intervention. Results We followed up 99 patients (47 in the PRP group and 52 in the CS group) until 12 months after injection. There were no differences in baseline patient demographic characteristics including age, sex, or duration of symptoms. Despite randomization, patients in the PRP group had worse baseline VAS (46.0 vs 34.7, P = .01), ASES (53.9 vs 61.8, P = .02), and WORC (42.2 vs 49.5, P = .03) scores. At 3 months after injection, the PRP group had superior improvement in VAS (–13.6 vs 0.4, P = .03), ASES (13.0 vs 2.9, P = .02), and WORC (16.8 vs 5.8, P = .03) scores. There were no differences in patient-reported outcomes at 6 weeks or 12 months. There was no difference in the rate of failure (P = .31) or conversion to surgery (P = .83) between groups. Conclusions Patients with PTRCTs or tendinopathy experienced clinical improvement in pain and patient-reported outcome scores after both ultrasound-guided CS and PRP injections. Patients who received PRP obtained superior improvement in pain and function at short-term follow-up (3 months). There was no sustained benefit of PRP over CS at longer-term follow-up (12 months). Level of Evidence Level I, randomized controlled trial.

Platelet-Rich Plasma in Patients With Partial-Thickness Rotator Cuff Tears or Tendinopathy Leads to Significantly Improved Short-Term Pain Relief and Function Compared With Corticosteroid Injection: A Double-Blind Randomized Controlled Trial

This review evaluates current clinical literature on the use of platelet-rich plasma (PRP), including leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP), in order to develop evidence-based recommendations for various musculoskeletal indications. Abundant high-quality evidence supports the use of LR-PRP injection for lateral epicondylitis and LP-PRP for osteoarthritis of the knee. Moderate high-quality evidence supports the use of LR-PRP injection for patellar tendinopathy and of PRP injection for plantar fasciitis and donor site pain in patellar tendon graft BTB ACL reconstruction. There is insufficient evidence to routinely recommend PRP for rotator cuff tendinopathy, osteoarthritis of the hip, or high ankle sprains. Current evidence demonstrates a lack of efficacy of PRP for Achilles tendinopathy, muscle injuries, acute fracture or nonunion, surgical augmentation in rotator cuff repair, Achilles tendon repair, and ACL reconstruction. PRP is a promising treatment for some musculoskeletal diseases; however, evidence of its efficacy has been highly variable depending on the specific indication. Additional high-quality clinical trials with longer follow-up will be critical in shaping our perspective of this treatment option.

Current Clinical Recommendations for Use of Platelet-Rich Plasma.

Platelet-Rich Plasma.

INTRODUCTION Approximately 10% of men and 13% of women older than the age of 60 are affected by symptomatic osteoarthritis of the knee. Anatomic repair or reconstruction after knee injury has been a central tenet of surgical treatment to reduce the risk of osteoarthritis. The purpose of this study was to examine common sports medicine procedures of the knee and determine the proportion of patients who subsequently undergo total knee arthroplasty (TKA). METHODS The MarketScan database was queried from the period of January 2007 through December 2016. Patients were identified, who underwent a procedure of the knee, as defined by Current Procedural Terminology codes relating to nonarthroplasty procedures of the knee. Patients in whom laterality could not be confirmed or underwent another ipsilateral knee procedure before TKA were excluded from this study. The primary outcome of this study was the overall rate of TKA after index knee surgery. Time from index procedure to TKA was a secondary outcome. A multivariate regression analysis was used to control for covariates such as age, sex, and comorbidity status. RESULTS A total of 843,749 patients underwent one of the 13 common sports medicine procedures of the knee. The procedure with the highest unadjusted rate of subsequent TKA was arthroscopic osteochondral allograft (5.81%), whereas anterior cruciate ligament (ACL) reconstruction with meniscus repair demonstrated the lowest rate of subsequent TKA (0.01%). When adjusting for confounding factors, the regression analysis identified meniscal transplantation (odds ratio [OR] = 3.06, P < 0.0001) as having the highest risk of subsequent TKA, followed by osteochondral autograft (OR = 1.74, P = 0.0424) and arthroscopic osteochondral allograft (OR = 1.49, P < 0.0001). ACL reconstruction with meniscus repair (OR = 0.02, P < 0.0001), ACL reconstruction alone (OR = 0.17, P < 0.0001), ACL with meniscectomy (OR = 0.20, P < 0.0001), and meniscal repair (OR = 0.65, P < 0.0001) had the lowest rate of subsequent TKA. ACL reconstruction with meniscus repair had the longest period from index procedure to TKA at 2827 days. CONCLUSION ACL reconstruction and meniscus preservation demonstrated an extremely low rate of conversion to TKA when compared with patients who needed salvage interventions such as meniscus and cartilage transplantation. None of the salvage interventions delayed the need for a TKA. Meniscal transplantation had the highest risk of all procedures of going on to a TKA.

Lawrence Enweze

Papers

Current Clinical Recommendations for Use of Platelet-Rich Plasma.

Platelet-Rich Plasma.

Risk of Subsequent Knee Arthroplasty After Sports Medicine Procedures.