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      Cell sources proposed for nucleus pulposus regeneration

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          Abstract

          Lower back pain (LBP) occurs in 80% of adults in their lifetime; resulting in LBP being one of the biggest causes of disability worldwide. Chronic LBP has been linked to the degeneration of the intervertebral disc (IVD). The current treatments for chronic back pain only provide alleviation of symptoms through pain relief, tissue removal, or spinal fusion; none of which target regenerating the degenerate IVD. As nucleus pulposus (NP) degeneration is thought to represent a key initiation site of IVD degeneration, cell therapy that specifically targets the restoration of the NP has been reviewed here. A literature search to quantitatively assess all cell types used in NP regeneration was undertaken. With key cell sources: NP cells; annulus fibrosus cells; notochordal cells; chondrocytes; bone marrow mesenchymal stromal cells; adipose‐derived stromal cells; and induced pluripotent stem cells extensively analyzed for their regenerative potential of the NP. This review highlights: accessibility; expansion capability in vitro; cell survival in an IVD environment; regenerative potential; and safety for these key potential cell sources. In conclusion, while several potential cell sources have been proposed, iPSC may provide the most promising regenerative potential.

          Abstract

          Cell sources and lineages proposed for regeneration of the intervertebral disc. This review highlights: accessibility; expansion capability in vitro; cell survival in an IVD environment; regenerative potential; and safety for these key potential cell sources. In conclusion, while several potential cell sources have been proposed, induced pluripotent stem cells may provide the most promising regenerative potential.

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          Most cited references264

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          Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

          Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to mouse embryonic development. These data demonstrate that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors.
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            What low back pain is and why we need to pay attention

            Low back pain is a very common symptom. It occurs in high-income, middle-income, and low-income countries and all age groups from children to the elderly population. Globally, years lived with disability caused by low back pain increased by 54% between 1990 and 2015, mainly because of population increase and ageing, with the biggest increase seen in low-income and middle-income countries. Low back pain is now the leading cause of disability worldwide. For nearly all people with low back pain, it is not possible to identify a specific nociceptive cause. Only a small proportion of people have a well understood pathological cause-eg, a vertebral fracture, malignancy, or infection. People with physically demanding jobs, physical and mental comorbidities, smokers, and obese individuals are at greatest risk of reporting low back pain. Disabling low back pain is over-represented among people with low socioeconomic status. Most people with new episodes of low back pain recover quickly; however, recurrence is common and in a small proportion of people, low back pain becomes persistent and disabling. Initial high pain intensity, psychological distress, and accompanying pain at multiple body sites increases the risk of persistent disabling low back pain. Increasing evidence shows that central pain-modulating mechanisms and pain cognitions have important roles in the development of persistent disabling low back pain. Cost, health-care use, and disability from low back pain vary substantially between countries and are influenced by local culture and social systems, as well as by beliefs about cause and effect. Disability and costs attributed to low back pain are projected to increase in coming decades, in particular in low-income and middle-income countries, where health and other systems are often fragile and not equipped to cope with this growing burden. Intensified research efforts and global initiatives are clearly needed to address the burden of low back pain as a public health problem.
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              Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians.

              The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on noninvasive treatment of low back pain.

                Author and article information

                Contributors
                c.lemaitre@shu.ac.uk
                Journal
                JOR Spine
                JOR Spine
                10.1002/(ISSN)2572-1143
                JSP2
                JOR Spine
                John Wiley & Sons, Inc. (Hoboken, USA )
                2572-1143
                24 November 2021
                December 2021
                : 4
                : 4 ( doiID: 10.1002/jsp2.v4.4 )
                : e1175
                Affiliations
                [ 1 ] Biomedical Research Centre, Biosciences Sheffield Hallam University Sheffield UK
                [ 2 ] Department of Clinical Sciences, Faculty of Veterinary Medicine Utrecht University Utrecht The Netherlands
                Author notes
                [*] [* ] Correspondence

                Christine Lyn Le Maitre, Biomedical Research Centre, Biosciences, Sheffield Hallam University, Sheffield S1 1WB, UK.

                Email: c.lemaitre@ 123456shu.ac.uk

                Author information
                https://orcid.org/0000-0002-2333-7162
                https://orcid.org/0000-0003-4489-7107
                Article
                JSP21175
                10.1002/jsp2.1175
                8717099
                35005441
                521c0ad9-e7b9-4c68-a947-6ae74a12570f
                © 2021 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 01 October 2021
                : 29 July 2021
                : 20 October 2021
                Page count
                Figures: 6, Tables: 1, Pages: 27, Words: 26185
                Funding
                Funded by: Dutch Arthritis Society , doi 10.13039/100018286;
                Award ID: LLP22
                Funded by: European Unions Horizon 2020 Research 52 and Innovation Program iPSpine , doi 10.13039/100010686;
                Award ID: 825925
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                December 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.7.0 mode:remove_FC converted:30.12.2021

                biologic therapies,regenerative medicine,stem cell,tissue engineering

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