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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 references52

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          Stem cell therapy for intervertebral disc regeneration: obstacles and solutions.

          Intervertebral disc (IVD) degeneration is frequently associated with low back and neck pain, which accounts for disability worldwide. Despite the known outcomes of the IVD degeneration cascade, the treatment of IVD degeneration is limited in that available conservative and surgical treatments do not reverse the pathology or restore the IVD tissue. Regenerative medicine for IVD degeneration, by injection of IVD cells, chondrocytes or stem cells, has been extensively studied in the past decade in various animal models of induced IVD degeneration, and has progressed to clinical trials in the treatment of various spinal conditions. Despite preliminary results showing positive effects of cell-injection strategies for IVD regeneration, detailed basic research on IVD cells and their niche indicates that transplanted cells are unable to survive and adapt in the avascular niche of the IVD. For this therapeutic strategy to succeed, the indications for its use and the patients who would benefit need to be better defined. To surmount these obstacles, the solution will be identified only by focused research, both in the laboratory and in the clinic.
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            MRI Findings of Disc Degeneration are More Prevalent in Adults with Low Back Pain than in Asymptomatic Controls: A Systematic Review and Meta-Analysis.

            Imaging features of spine degeneration are common in symptomatic and asymptomatic individuals. We compared the prevalence of MR imaging features of lumbar spine degeneration in adults 50 years of age and younger with and without self-reported low back pain.
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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 )
                : e1043
                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

                Author information
                https://orcid.org/0000-0001-7631-0476
                https://orcid.org/0000-0002-3281-4629
                https://orcid.org/0000-0001-7142-1660
                https://orcid.org/0000-0003-0459-9092
                https://orcid.org/0000-0002-0050-874X
                Article
                JSP21043
                10.1002/jsp2.1043
                6711491
                31463457
                a6d9e499-7ef7-4187-afc7-0e41748995ad
                © 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.

                History
                : 01 September 2018
                : 31 December 2018
                : 17 January 2019
                Page count
                Figures: 4, Tables: 1, Pages: 10, Words: 7217
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                jsp21043
                March 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.7 mode:remove_FC converted:05.08.2019

                degenerate disc disease,inflammation,intervertebral disc degeneration,mesenchymal stem cells,microenvironment,regeneration

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