Current understanding of MSC-derived exosomes in the management of knee osteoarthritis.

Mesenchymal stem cell-derived exosomes (MSC-Exos) have been utilized as medicinal agents or as delivery vehicles in cartilage injuries and cartilage-based diseases. Given the ongoing emergence of evidence on the effector mechanisms and methods of the utility of the MSC-Exos in knee osteoarthritis, a comprehensive review of the current evidence is the need of the hour. Hence, in this article, we review the current understanding of the role of MSC-Exos in the management of knee osteoarthritis in view of their classification, characterization, biogenesis, mechanism of action, pathways involved in their therapeutic action, in-vitro evidence on cartilage regeneration, in-vivo evidence in OA knee models and recent advances in using MSC-Exos to better streamline future research from bench to bedside for OA knee.

Ochrobactrum anthropi - An Emerging Opportunistic Pathogen in Musculoskeletal Disorders - A Case Report and Review of Literature.

Introduction: Ochrobactrum anthropi is an opportunistic and rare human pathogen, which is seen widely in the environment. O. anthropi infections have been reported in both immunocompetent and immunocompromised individuals. There is no proper consensus on the diagnosis and management of O. anthropi related infections. Case Report: We report a case of O. anthropi related left distal clavicular osteomyelitis in an immunocompetent individual with an elaborative diagnostic and treatment algorithm for its effective management. Conclusion: A comprehensive management strategy with a combination of implant removal (if present) with extensive surgical debridement of bone and soft tissue and intravenous antibiotics results in successful eradication of O. anthropi infection.

Impact of the Process Variables on the Yield of Mesenchymal Stromal Cells from Bone Marrow Aspirate Concentrate.

Human bone marrow (BM) has been highlighted as a promising source of mesenchymal stromal cells (MSCs) containing various growth factors and cytokines that can be potentially utilized in regenerative procedures involving cartilage and bone. However, the proportion of MSCs in the nucleated cell population of BM is only around 0.001% to 0.01% thereby making the harvesting and processing technique crucial for obtaining optimal results upon its use in various regenerative processes. Although several studies in the literature have given encouraging results on the utility of BM aspiration concentrate (BMAC) in various regenerative procedures, there is a lack of consensus concerning the harvesting variables such as choice of anesthetic agent to be used, site of harvest, size of the syringe to be used, anticoagulant of choice, and processing variables such as centrifugation time, and speed. In this review article, we aim to discuss the variables in the harvesting and processing technique of BMAC and their impact on the yield of MSCs in the final concentrate obtained from them.

Is Culture Expansion Necessary in Autologous Mesenchymal Stromal Cell Therapy to Obtain Superior Results in the Management of Knee Osteoarthritis?-Meta-Analysis of Randomized Controlled Trials.

Study Design: Meta-analysis. Objectives: We aimed to analyze the impact of cultured expansion of autologous mesenchymal stromal cells (MSCs) in the management of osteoarthritis of the knee from randomized controlled trials (RCTs) available in the literature. Materials and Methods: We conducted independent and duplicate electronic database searches including PubMed, Embase, Web of Science, and Cochrane Library until August 2021 for RCTs analyzing the efficacy and safety of culture-expanded compared to non-cultured autologous MSCs in the management of knee osteoarthritis. The Visual Analog Score (VAS) for pain, Western Ontario McMaster University's Osteoarthritis Index (WOMAC), Lysholm score, Knee Osteoarthritis Outcome Score (KOOS), and adverse events were the analyzed outcomes. Analysis was performed in R-platform using OpenMeta [Analyst] software. Results: Overall, 17 studies involving 767 patients were included for analysis. None of the studies made a direct comparison of the culture expanded and non-cultured MSCs, hence we pooled the results of all the included studies of non-cultured and cultured types of MSC sources and made a comparative analysis of the outcomes. At six months, culture expanded MSCs showed significantly better improvement (p < 0.001) in VAS outcome. Uncultured MSCs, on the other hand, demonstrated significant VAS improvement in the long term (12 months) in VAS (p < 0.001), WOMAC (p = 0.025), KOOS score (p = 0.016) where cultured-expanded MSCs failed to demonstrate a significant change. Culturing of MSCs did not significantly increase the complications noted (p = 0.485). On sub-group analysis, adipose-derived uncultured MSCs outperformed culture-expanded MSCs at both short term (six months) and long term (12 months) in functional outcome parameters such as WOMAC (p < 0.001, p = 0.025), Lysholm (p < 0.006), and KOOS (p < 0.003) scores, respectively, compared to their controls. Conclusions: We identified a void in literature evaluating the impact of culture expansion of MSCs for use in knee osteoarthritis. Our indirect analysis of literature showed that culture expansion of autologous MSCs is not a necessary factor to obtain superior results in the management of knee osteoarthritis. Moreover, while using uncultured autologous MSCs, we recommend MSCs of adipose origin to obtain superior functional outcomes. However, we urge future trials of sufficient quality to validate our findings to arrive at a consensus on the need for culture expansion of MSCs for use in cellular therapy of knee osteoarthritis.