Mesenchymal stem cell-derived extracellular vesicles, osteoimmunology and orthopedic diseases.

Mesenchymal stem cells (MSCs) play an important role in tissue healing and regenerative medicine due to their self-renewal and multi-directional differentiation properties. MSCs exert their therapeutic effects mainly via the paracrine pathway, which involves the secretion of extracellular vesicles (EVs). EVs have a high drug loading capacity and can transport various molecules, such as proteins, nucleic acids, and lipids, that can modify the course of diverse diseases. Due to their ability to maintain the therapeutic effects of their parent cells, MSC-derived EVs have emerged as a promising, safe cell-free treatment approach for tissue regeneration. With advances in inflammation research and emergence of the field of osteoimmunology, evidence has accumulated pointing to the role of inflammatory and osteoimmunological processes in the occurrence and progression of orthopedic diseases. Several studies have shown that MSC-derived EVs participate in bone regeneration and the pathophysiology of orthopedic diseases by regulating the inflammatory environment, enhancing angiogenesis, and promoting the differentiation and proliferation of osteoblasts and osteoclasts. In this review, we summarize recent advances in the application and functions of MSC-derived EVs as potential therapies against orthopedic diseases, including osteoarthritis, intervertebral disc degeneration, osteoporosis and osteonecrosis.

Associations between smoking and clinical outcomes after total hip and knee arthroplasty: A systematic review and meta-analysis.

Background: Smoking increases risk of several complications after total hip or knee arthroplasty (THA/TKA), so we systematically reviewed and meta-analyzed the literature to take into account all relevant evidence, particularly studies published since 2010. Methods: The PubMed, Ovid Embase, Web of Science, and EBSCOHost databases were searched and studies were selected and analyzed according to MOOSE recommendations. Methodological quality of included studies was assessed using the Newcastle-Ottawa Scale. Data were qualitatively synthesized or meta-analyzed using a random-effects model. Results: A total of 40 studies involving 3,037,683 cases were included. Qualitative analysis suggested that smoking is associated with worse patient-reported outcomes within one year after surgery, and meta-analysis showed that smoking significantly increased risk of the following outcomes: total complications (OR 1.41, 95% CI 1.01-1.98), wound complications (OR 1.77, 95% CI 1.50-2.10), prosthetic joint infection (OR 1.84, 95% CI 1.52-2.24), aseptic loosening (OR 1.62, 95% CI 1.12-2.34), revision (OR 2.12, 95% CI 1.46-3.08), cardiac arrest (OR 4.90, 95% CI 2.26-10.60), cerebrovascular accident (OR 2.22, 95% CI 1.01-4.85), pneumonia (OR 2.35, 95% CI 1.17-4.74), acute renal insufficiency (OR 2.01, 95% CI 1.48-2.73), sepsis (OR 4.35, 95% CI 1.35-14.00), inpatient mortality (OR 12.37, 95% CI 4.46-34.28), and persistent opioid consumption (OR 1.64, 95% CI 1.39-1.92). Conclusion: Smoking patients undergoing THA and TKA are at increased risk of numerous complications, inpatient mortality, persistent opioid consumption, and worse 1-year patient-reported outcomes. Pre-surgical protocols for these outcomes should give special consideration to smoking patients.

The Dynamic Feature of Macrophage M1/M2 Imbalance Facilitates the Progression of Non-Traumatic Osteonecrosis of the Femoral Head.

Non-traumatic osteonecrosis of the femoral head (NONFH) remains a common refractory disease with poorly understood pathogenesis. Macrophage M1/M2 imbalance and chronic inflammatory microenvironment have been suggested to be closely related to osteonecrosis. Here we describe direct visual evidence for the involvement of dynamic changes in macrophages and the chronic inflammatory microenvironment in human NONFH. Osteonecrosis induces inflammatory responses and macrophage enrichment in the reparative area, and the number of inflammatory cells and macrophages falls during progressive-to end-stage NONFH. Multiplex immunohistochemistry demonstrated that macrophage M1/M2 ratio increased from 3 to 10 during progressive-to end-stage. During the progressive-stage, new blood vessels formed in the reparative area, M2 macrophages accumulated in perivascular (M1/M2 ratio ∼0.05), while M1 macrophages were enriched in avascular areas (M1/M2 ratio ∼12). Furthermore, inflammatory cytokines were detected in synovial fluid and plasma using cytometric bead arrays. Interleukin (IL)-6 and IL-1ß were persistently enriched in synovial fluid compared to plasma in patients with NONFH, and this difference was confirmed by immunohistochemistry staining. However, only IL-6 levels in plasma were higher in patients with progressive-stage NONFH than in osteoarthritis. Moreover, fibrosis tissues were observed in the necrotic area in progressive-stage and end-stage NONFH based on Sirius Red staining. Together, these findings indicate that macrophage M1/M2 imbalance facilitates the progression of NONFH, a chronic inflammatory disease characterized by chronic inflammation, osteonecrosis and tissue fibrosis in the local lesion. Inhibiting inflammation, promoting the resolution of inflammation, switching macrophages to an M2 phenotype, or inhibiting their adoption of an M1 phenotype may be useful therapeutic strategies against NONFH.

Effectiveness and safety of traditional Chinese medicine in the treatment of steroid-osteonecrosis of femoral head: A protocol for systematic review and meta-analysis.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common refractory disease in orthopedics. Overdose glucocorticoid application is a common trigger for ONFH. Traditional Chinese medicine (TCM), as a treatment for ONFH, has been shown to be effective in treating steroid-induced ONFH (SONFH). However, a systematic review and meta-analysis of them is lacking. We aim to systematically review the effectiveness and safety of TCM in the treatment of SONFH. METHODS: We will search the following databases: PubMed, Embase, the Cochrane Library, MEDLINE, the Chinese Biomedical Literature Database, China Science and Technology Journal Database, China National Knowledge Infrastructure, and Wanfang Data (since the inception of the databases to the present). In addition, we will look for clinical trial registrations, prospective grey literature, relevant conference papers, and established study reference lists. We will use Review Manager 5.3 software for meta-analysis and heterogeneity assessment. We will evaluate the quality of the evidence using a hierarchy of recommendation assessment, development, and evaluation. RESULTS: This study will systematically evaluate the efficacy and safety of TCM in the treatment of SONFH. CONCLUSION: This systematic review to evaluate the effectiveness and safety of TCM in the treatment of SONFH will provide updated evidence for clinical application. INPLASY REGISTRATION NUMBER: INPLASY202170015.