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      Controversies in regenerative medicine: Should intervertebral disc degeneration be treated with mesenchymal stem cells?

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          Abstract

          Low back pain (LBP) can significantly reduce the quality of life of patients, and has a considerable economic and social impact worldwide. It is commonly associated with disc degeneration, even though many people with degenerate discs are asymptomatic. Degenerate disc disease (DDD), is thus a common term for intervertebral disc (IVD) degeneration associated with LBP. Degeneration is thought to lead to LBP because of nerve ingrowth into the degenerate disc, inflammation, or because degradation of extracellular matrix (ECM) alters spinal biomechanics inappropriately. Thus, while the objectives of some interventions for LBP are to control pain intensity, other interventions aim to deal with the consequences of disc degeneration through stabilizing the disc surgically, by inserting artificial discs or by repairing the disc biologically and preventing progressive IVD degeneration. Despite tremendous research efforts, treatment of LBP through the use of regenerative interventions aiming to repair the IVD is still controversial. The use of mesenchymal stem cells for IVD regeneration in a patient‐based case will be discussed by an ensemble of clinicians and researchers.

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          Most cited references 57

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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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            The global burden of low back pain: estimates from the Global Burden of Disease 2010 study.

            To estimate the global burden of low back pain (LBP). LBP was defined as pain in the area on the posterior aspect of the body from the lower margin of the twelfth ribs to the lower glutaeal folds with or without pain referred into one or both lower limbs that lasts for at least one day. Systematic reviews were performed of the prevalence, incidence, remission, duration, and mortality risk of LBP. Four levels of severity were identified for LBP with and without leg pain, each with their own disability weights. The disability weights were applied to prevalence values to derive the overall disability of LBP expressed as years lived with disability (YLDs). As there is no mortality from LBP, YLDs are the same as disability-adjusted life years (DALYs). Out of all 291 conditions studied in the Global Burden of Disease 2010 Study, LBP ranked highest in terms of disability (YLDs), and sixth in terms of overall burden (DALYs). The global point prevalence of LBP was 9.4% (95% CI 9.0 to 9.8). DALYs increased from 58.2 million (M) (95% CI 39.9M to 78.1M) in 1990 to 83.0M (95% CI 56.6M to 111.9M) in 2010. Prevalence and burden increased with age. LBP causes more global disability than any other condition. With the ageing population, there is an urgent need for further research to better understand LBP across different settings.
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              Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study.

              Degenerative disc disease may cause severe low-back pain, a large public health problem with significant economic and life quality impact. Chronic cases often require surgery, which may lead to biomechanical problems and accelerated degeneration of the adjacent segments. Cell-based therapies may circumvent these problems and have exhibited encouraging results in vitro and in animal studies. We designed a pilot study to assess feasibility and safety and to obtain early indications on efficacy of treatment with mesenchymal stem cells (MSC) in humans. Ten patients with chronic back pain diagnosed with lumbar disc degeneration with intact annulus fibrosus were treated with autologous expanded bone marrow MSC injected into the nucleus pulposus area. Clinical evolution was followed for 1 year and included evaluation of back pain, disability, and quality of life. Magnetic resonance imaging measurements of disc height and fluid content were also performed. Feasibility and safety were confirmed and strong indications of clinical efficacy identified. Patients exhibited rapid improvement of pain and disability (85% of maximum in 3 months) that approached 71% of optimal efficacy. This outcome compares favorably with the results of other procedures such as spinal fusion or total disc replacement. Although disc height was not recovered, water content was significantly elevated at 12 months. MSC therapy may be a valid alternative treatment for chronic back pain caused by degenerative disc disease. Advantages over current gold standards include simpler and more conservative intervention without surgery, preservation of normal biomechanics, and same or better pain relief.
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                Author and article information

                Contributors
                markus.loibl@gmail.com
                Journal
                JOR Spine
                JOR Spine
                10.1002/(ISSN)2572-1143
                JSP2
                JOR Spine
                John Wiley & Sons, Inc. (Hoboken, USA )
                2572-1143
                01 March 2019
                March 2019
                : 2
                : 1 ( doiID: 10.1002/jsp2.2019.2.issue-1 )
                Affiliations
                [ 1 ] Department of Spine Surgery Schulthess Klinik Zürich Switzerland
                [ 2 ] Department of Trauma Surgery Regensburg University Medical Center Regensburg Germany
                [ 3 ] Institute for Biomechanics, Department of Health Sciences and Technology ETH Zürich, Zürich Switzerland
                [ 4 ] Spine Center, Schön Klinik München Munich Germany
                [ 5 ] Academic Teaching Hospital and Spine Research Institute Paracelsus Private Medical University Salzburg Austria
                [ 6 ] Department of Health Science University of Potsdam Potsdam Germany
                [ 7 ] Department of Orthopaedic and Trauma Surgery Campus Bio‐Medico University of Rome Rome Italy
                [ 8 ] Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford Oxford UK
                [ 9 ] Department of Physiology, Anatomy and Genetics University of Oxford Oxford UK
                Author notes
                [* ] Correspondence

                Dr Markus Loibl, Department of Spine Surgery, Schulthess Klinik, Lengghalde 2, 8008 Zürich, Switzerland.

                Email: markus.loibl@ 123456gmail.com

                Article
                JSP21043
                10.1002/jsp2.1043
                6711491
                © 2019 The Authors. JOR Spine published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 4, Tables: 1, Pages: 10, Words: 7217
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                Custom metadata
                2.0
                jsp21043
                March 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.7 mode:remove_FC converted:05.08.2019

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