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      Responses of human adipose-derived mesenchymal stem cells to chemical microenvironment of the intervertebral disc

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          Abstract

          Background

          Human adipose-derived mesenchymal stem cells (ADMSCs) may be ideal source of cells for intervertebral disc (IVD) regeneration, but the harsh chemical microenvironment of IVD may significantly influence the biological and metabolic vitality of ADMSCs and impair their repair potential. This study aimed to investigate the viability, proliferation and the expression of main matrix proteins of ADMSCs in the chemical microenvironment of IVD under normal and degeneration conditions.

          Methods

          ADMSCs were harvested from young (aged 8-12 years, n = 6) and mature (aged 33-42 years, n = 6) male donors and cultured under standard condition and IVD-like conditions (low glucose, acidity, high osmolarity, and combined conditions) for 2 weeks. Cell viability was measured by annexin V-FITC and PI staining and cell proliferation was measured by MTT assay. The expression of aggrecan and collagen-I was detected by real-time quantitative polymerase chain reaction and Western blot analysis.

          Results

          IVD-like glucose condition slightly inhibited cell viability, but increased the expression of aggrecan. In contrast, IVD-like osmolarity, acidity and the combined conditions inhibited cell viability and proliferation and the expression of aggrecan and collagen-I. ADMSCs from young and mature donors exhibited similar responses to the chemical microenvironments of IVD.

          Conclusion

          IVD-like low glucose is a positive factor but IVD-like high osmolarity and low pH are deleterious factors that affect the survival and biological behaviors of ADMSCs. These findings may promote the translational research of ADMSCs in IVD regeneration for the treatment of low back pain.

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          Most cited references31

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          Low back pain in relation to lumbar disc degeneration.

          Cross-sectional magnetic resonance imaging (MRI) study. To study the relation of low back pain (LBP) to disc degeneration in the lumbar spine. Controversy still prevails about the relationship between disc degeneration and LBP. Classification of disc degeneration and symptoms varies, hampering comparison of study results. Subjects comprised 164 men aged 40-45 years-53 machine drivers, 51 construction carpenters, and 60 office workers. The data of different types of LBP, individual characteristics, and lifestyle factors were obtained from a questionnaire and a structured interview. Degeneration of discs L2/L3-L5/S1 (dark nucleus pulposus and posterior and anterior bulge) was assessed with MRI. An increased risk of LBP (including all types) was found in relation to all signs of disc degeneration. An increased risk of sciatic pain was found in relation to posterior bulges, but local LBP was not related to disc degeneration. The risks of LBP and sciatic pain were strongly affected by occupation. Low back pain is associated with signs of disc degeneration and sciatic pain with posterior disc bulges. Low back pain is strongly associated with occupation.
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            Degeneration and regeneration of the intervertebral disc: lessons from development

            Degeneration of the intervertebral discs, a process characterized by a cascade of cellular, biochemical, structural and functional changes, is strongly implicated as a cause of low back pain. Current treatment strategies for disc degeneration typically address the symptoms of low back pain without treating the underlying cause or restoring mechanical function. A more in-depth understanding of disc degeneration, as well as opportunities for therapeutic intervention, can be obtained by considering aspects of intervertebral disc development. Development of the intervertebral disc involves the coalescence of several different cell types through highly orchestrated and complex molecular interactions. The resulting structures must function synergistically in an environment that is subjected to continuous mechanical perturbation throughout the life of an individual. Early postnatal changes, including altered cellularity, vascular regression and altered extracellular matrix composition, might set the disc on a slow course towards symptomatic degeneration. In this Perspective, we review the pathogenesis and treatment of intervertebral disc degeneration in the context of disc development. Within this scope, we examine how model systems have advanced our understanding of embryonic morphogenesis and associated molecular signaling pathways, in addition to the postnatal changes to the cellular, nutritional and mechanical microenvironment. We also discuss the current status of biological therapeutic strategies that promote disc regeneration and repair, and how lessons from development might provide clues for their refinement.
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              Adipose-Derived Mesenchymal Stem Cell Protects Kidneys against Ischemia-Reperfusion Injury through Suppressing Oxidative Stress and Inflammatory Reaction

              Background Reactive oxygen species are important mediators exerting toxic effects on various organs during ischemia-reperfusion (IR) injury. We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) protect the kidney against oxidative stress and inflammatory stimuli in rat during renal IR injury. Methods Adult male Sprague-Dawley (SD) rats (n = 24) were equally randomized into group 1 (sham control), group 2 (IR plus culture medium only), and group 3 (IR plus immediate intra-renal administration of 1.0 × 106 autologous ADMSCs, followed by intravenous ADMSCs at 6 h and 24 h after IR). The duration of ischemia was 1 h, followed by 72 hours of reperfusion before the animals were sacrificed. Results Serum creatinine and blood urea nitrogen levels and the degree of histological abnormalities were markedly lower in group 3 than in group 2 (all p < 0.03). The mRNA expressions of inflammatory, oxidative stress, and apoptotic biomarkers were lower, whereas the anti-inflammatory, anti-oxidative, and anti-apoptotic biomarkers were higher in group 3 than in group 2 (all p < 0.03). Immunofluorescent staining showed a higher number of CD31+, von Willebrand Factor+, and heme oxygenase (HO)-1+ cells in group 3 than in group 2 (all p < 0.05). Western blot showed notably higher NAD(P)H quinone oxidoreductase 1 and HO-1 activities, two indicators of anti-oxidative capacity, in group 3 than those in group 2 (all p < 0.04). Immunohistochemical staining showed higher glutathione peroxidase and glutathione reductase activities in group 3 than in group 2 (all p < 0.02) Conclusion ADMSC therapy minimized kidney damage after IR injury through suppressing oxidative stress and inflammatory response.
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                Author and article information

                Journal
                J Transl Med
                J Transl Med
                Journal of Translational Medicine
                BioMed Central
                1479-5876
                2012
                16 March 2012
                : 10
                : 49
                Affiliations
                [1 ]Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, No. 88 Jie fang Road, Hangzhou 310009, China
                Article
                1479-5876-10-49
                10.1186/1479-5876-10-49
                3338074
                22424131
                591db617-e505-4c1f-8d42-28ac5ba31c12
                Copyright ©2012 Liang et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 9 January 2012
                : 16 March 2012
                Categories
                Research

                Medicine
                intervertebral disc,chemical microenvironment,adipose-derived mesenchymal stem cells

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