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      Intraarticular injection of bone marrow-derived mesenchymal stem cells enhances regeneration in knee osteoarthritis

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          Abstract

          Purpose

          This review aimed to evaluate the efficacy of intra-articular injections of bone marrow derived mesenchymal stem cells (BM-MSCs) for the treatment of knee osteoarthritis (KOA).

          Methods

          This narrative review evaluates recent English language clinical data and published research articles between 2014 and 2019. Key word search strings of (((“bone marrow-derived mesenchymal stem cell” OR “bone marrow mesenchymal stromal cell” OR “bone marrow stromal cell”)) AND (“osteoarthritis” OR “knee osteoarthritis”)) AND (“human” OR “clinical”))) AND “intra-articular injection” were used to identify relevant articles using PMC, Cochrane Library, Web Of Science and Scopus databases.

          Results

          Pre-clinical studies have demonstrated successful, safe and encouraging results for articular cartilage repair and regeneration. This is concluded to be due to the multilineage differential potential, immunosuppressive and self-renewal capabilities of BM-MSCs, which have shown to augment pain and improve functional outcomes. Subsequently, clinical applications of intra-articular injections of BM-MSCs are steadily increasing, with most studies demonstrating a decrease in poor cartilage index, improvements in pain, function and Quality of Life (QoL); with moderate-to-high level evidence regarding safety for therapeutic administration. However, low confidence in clinical efficacy remains due to a plethora of heterogenous methodologies utilised, resulting in challenging study comparisons. A moderate number of cells (40 × 10 6) were identified as most likely to achieve optimal responses in individuals with grade ≥ 2 KOA. Likewise, significant improvements were reported when using lower (24 × 10 6) and higher (100 × 10 6) cell numbers, although adverse effects including persistent pain and swelling were a consequence.

          Conclusion

          Overall, the benefits of intra-articular injections of BM-MSCs were deemed to outweigh the adverse effects; thus, this treatment be considered as a future therapy strategy. To realise this, long-term large-scale randomised clinical trials are required to enable improved interpretations, to determine the validity of efficacy in future studies.

          Level of evidence

          IV.

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          Most cited references65

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          Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.

          The considerable therapeutic potential of human multipotent mesenchymal stromal cells (MSC) has generated markedly increasing interest in a wide variety of biomedical disciplines. However, investigators report studies of MSC using different methods of isolation and expansion, and different approaches to characterizing the cells. Thus it is increasingly difficult to compare and contrast study outcomes, which hinders progress in the field. To begin to address this issue, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy proposes minimal criteria to define human MSC. First, MSC must be plastic-adherent when maintained in standard culture conditions. Second, MSC must express CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79alpha or CD19 and HLA-DR surface molecules. Third, MSC must differentiate to osteoblasts, adipocytes and chondroblasts in vitro. While these criteria will probably require modification as new knowledge unfolds, we believe this minimal set of standard criteria will foster a more uniform characterization of MSC and facilitate the exchange of data among investigators.
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            Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

            Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013.
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              The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study.

              To estimate the global burden of hip and knee osteoarthritis (OA) as part of the Global Burden of Disease 2010 study and to explore how the burden of hip and knee OA compares with other conditions. Systematic reviews were conducted to source age-specific and sex-specific epidemiological data for hip and knee OA prevalence, incidence and mortality risk. The prevalence and incidence of symptomatic, radiographic and self-reported hip or knee OA were included. Three levels of severity were defined to derive disability weights (DWs) and severity distribution (proportion with mild, moderate and severe OA). The prevalence by country and region was multiplied by the severity distribution and the appropriate disability weight to calculate years of life lived with disability (YLDs). As there are no deaths directly attributed to OA, YLDs equate disability-adjusted life years (DALYs). Globally, of the 291 conditions, hip and knee OA was ranked as the 11th highest contributor to global disability and 38th highest in DALYs. The global age-standardised prevalence of knee OA was 3.8% (95% uncertainty interval (UI) 3.6% to 4.1%) and hip OA was 0.85% (95% UI 0.74% to 1.02%), with no discernible change from 1990 to 2010. Prevalence was higher in females than males. YLDs for hip and knee OA increased from 10.5 million in 1990 (0.42% of total DALYs) to 17.1 million in 2010 (0.69% of total DALYs). Hip and knee OA is one of the leading causes of global disability. Methodological issues within this study make it highly likely that the real burden of OA has been underestimated. With the aging and increasing obesity of the world's population, health professions need to prepare for a large increase in the demand for health services to treat hip and knee OA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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                Author and article information

                Contributors
                s.wilson2@lboro.ac.uk
                Journal
                Knee Surg Sports Traumatol Arthrosc
                Knee Surg Sports Traumatol Arthrosc
                Knee Surgery, Sports Traumatology, Arthroscopy
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0942-2056
                1433-7347
                31 January 2020
                31 January 2020
                2020
                : 28
                : 12
                : 3827-3842
                Affiliations
                [1 ]GRID grid.6571.5, ISNI 0000 0004 1936 8542, National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, , Loughborough University, ; Epinal Way, Loughborough, LE11 3TU Leicestershire UK
                [2 ]GRID grid.6571.5, ISNI 0000 0004 1936 8542, Centre for Biological Engineering, Wolfson School of Mechanical, Electrical and Manufacturing Engineering, , Loughborough University, ; Epinal Way, Loughborough, LE11 3TU Leicestershire UK
                Author information
                http://orcid.org/0000-0002-9152-9182
                Article
                5859
                10.1007/s00167-020-05859-z
                7669782
                32006075
                5a46db58-91d5-47af-8cf8-b47155fb2515
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 July 2019
                : 16 January 2020
                Categories
                Knee
                Custom metadata
                © European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA) 2020

                Surgery
                allogenic,autologous,cell therapies,clinical efficacy,immunomodulation,mesenchymal stem cells,optimal dosage,osteoarthritis

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