Background. The use of laboratory-expanded mesenchymal stem cells (MSCs) is subject to several restrictions, resulting in “minimal manipulation” methods becoming the current most popular strategy to increase the use of MSCs in an orthopaedic practice. The aim of the present systematic review is to assess the clinical applications of “minimally” manipulated MSCs, either as bone marrow aspirate concentrate (BMAC) or as stromal vascular fraction (SVF), in the treatment of knee osteoarthritis (OA). Methods. A systematic review of three databases (PubMed, ScienceDirect, and Google Scholar) was performed using the following keywords: “Knee Osteoarthritis” with “(Bone marrow aspirate) OR (bone marrow concentrate)” or with “(adipose-derived mesenchymal stem cells) OR (adipose derived stromal cells) OR (stromal vascular fraction) OR (SVF)” as either keywords or MeSH terms. The reference lists of all retrieved articles were further reviewed for identification of potentially relevant studies. Results. Twenty-three papers were included in the final analysis (10 on BMAC and 13 on SVF). Of these, only 4 were randomized controlled trials (RCTs). Bias risk evaluation, performed using a modified Coleman score, revealed an overall poor quality of the studies. In terms of clinical application, despite the apparent safety of minimally manipulated MSCs and the short-term positive clinical outcomes associated with their use, clinicians reported different preparation and administration methods, ranging from single intra-articular injections to intraosseous applications to administration in combination with other surgical procedures. Conclusions. The available literature is undermined by both the lack of high-quality studies and the varied clinical settings and different protocols reported in the few RCTs presently published. This prevents any recommendation on the use of either product in a clinical practice. Nevertheless, the use of minimally manipulated MSCs (in the form of BMAC or SVF) has been shown to be safe and have some short-term beneficial effects.

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Prosthetic joint infection (PJI) management is not standardized worldwide and the outcome is frequently unsatisfactory.More and more arthroplasties are now being performed. An increasing number of highly virulent and antibiotic-resistant bacteria and an ageing population of patients presenting with many comorbidities make it necessary to focus on this important topic.Diagnosis of PJI remains challenging because the clinical signs and symptoms and elevation of systemic biomarkers (C-reactive protein, erythrocyte sedimentation rate) may be unclear.In the last few years, the clinical research has focused on synovial fluid biomarkers as a possible breakthrough in the complex scenario of PJI diagnosis.Synovial biomarkers have shown encouraging results and they should be used as diagnostic adjuncts to synovial white cell count and culture bacteriology. Synovial leukocyte esterase (LE) and synovial C-reactive protein (CRP) have been evaluated as good screening measures; however, the most promising synovial fluid biomarker in terms of sensitivity and specificity for PJI seems to be alpha defensin (AD).The laboratory-based alpha defensin enzyme-linked immunosorbent assay (ELISA) test demonstrated the highest ever reported accuracy for PJI diagnosis. However, an alpha defensin lateral flow test could have its place in ruling in a suspected PJI intraoperatively because of its high specificity and rapid results.Cite this article: EFORT Open Rev 2019;4:10-13. DOI: 10.1302/2058-5241.4.180029

Osteoarthritis (OA) is one of the most common causes of chronic disability in adults due to pain and altered joint function. Although most patients report pain and functional limitation, symptoms, age of onset and disease progression are extremely variable. While inflammation could play a central role in the OA pathogenesis and progression, many underpinning mechanisms are still unclear. A number of proinflammatory mediators have been found in OA joints and could play a role, such as IL-1, IL-6, IL-7, IL-8, IL-15, IL-17, IL-18, TNF-alpha, macrophage chemotactic protein (MCP)-1, interferon-induced protein (IP)-10, monokine induced by interferon (MIG), oncostatin M (OSM), growth-related oncogene (GRO)alpha, chemokine (C-C-motif) ligand 19 (CCL19), macrophage inflammatory protein (MIP)-1beta, and TGF-alpha. Biological approaches have recently got increasing interest due to their anti-inflammatory and immunomodulatory properties, regenerative potential, and high tolerability. The primary aim of this paper is to report the current concepts on regenerative medicine for knee OA with a particular focus on Autologous Protein solution (APS). APS is a blood derived product obtained by using a proprietary device, made of APS Separator, which isolates WBCs and platelets in a small volume of plasma, and APS Concentrator, which further concentrates platelets, WBCs and plasma proteins. The result is a peculiar formulation differing from other biologic products as it contains high levels of growth factors (EGF, IGF-1, PDGF-AB, PDGF-BB, VEGF, TGF-b1) along with high concentrations of anti-inflammatory mediators (IL-1ra, sIL-1RII, sTNF-RI, sTNF-RII) and low levels of pro-inflammatory cytokines (Il-1b and TNF-a). While emerging evidence supports the use of APS, as confirmed by in vitro studies and preliminary clinical results, the real clinical potential of APS and its benefits are still under investigation.

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