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      Multi-compositional MRI evaluation of repair cartilage in knee osteoarthritis with treatment of allogeneic human adipose-derived mesenchymal progenitor cells

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          Abstract

          Background

          We used multimodal compositional magnetic resonance imaging (MRI) techniques, combined with clinical outcomes, to differentiate the alternations of composition in repair cartilage with allogeneic human adipose-derived mesenchymal progenitor cells (haMPCs) in knee osteoarthritis (KOA) patients.

          Methods

          Eighteen patients participated a phase I/IIa clinical trial. All patients were divided randomly into three groups with intra-articular injections of haMPCs: the low-dose (1.0 × 10 7 cells), mid-dose (2.0 × 10 7), and high-dose (5.0 × 10 7) groups with six patients each. Compositional MRI examinations and clinical evaluations were performed at different time points.

          Results

          Significant differences were observed in quantitative T1rho, T2, T2star, R2star, and ADC measurements in patients of three dose groups, suggesting a possible compositional changes of cartilage with the treatment of allogeneic haMPCs. Also significant reduction in WOMAC and SF-36 scores showed the symptoms might be alleviated to some extent with this new treatment. As regards sensibilities of multi-parametric mappings to detect compositional or structural changes of cartilage, T1rho mapping was most sensitive to differentiate difference between three dose groups.

          Conclusions

          These results showed that multi-compositional MRI sequences might be an effective tool to evaluate the promotion of the repair of cartilage with allogeneic haMPCs by providing information of compositional alterations of cartilage.

          Trial registration

          Clinicaltrials, NCT02641860. Registered 3 December 2015.

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          Most cited references55

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          OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines.

          To develop concise, patient-focussed, up to date, evidence-based, expert consensus recommendations for the management of hip and knee osteoarthritis (OA), which are adaptable and designed to assist physicians and allied health care professionals in general and specialist practise throughout the world. Sixteen experts from four medical disciplines (primary care, rheumatology, orthopaedics and evidence-based medicine), two continents and six countries (USA, UK, France, Netherlands, Sweden and Canada) formed the guidelines development team. A systematic review of existing guidelines for the management of hip and knee OA published between 1945 and January 2006 was undertaken using the validated appraisal of guidelines research and evaluation (AGREE) instrument. A core set of management modalities was generated based on the agreement between guidelines. Evidence before 2002 was based on a systematic review conducted by European League Against Rheumatism and evidence after 2002 was updated using MEDLINE, EMBASE, CINAHL, AMED, the Cochrane Library and HTA reports. The quality of evidence was evaluated, and where possible, effect size (ES), number needed to treat, relative risk or odds ratio and cost per quality-adjusted life years gained were estimated. Consensus recommendations were produced following a Delphi exercise and the strength of recommendation (SOR) for propositions relating to each modality was determined using a visual analogue scale. Twenty-three treatment guidelines for the management of hip and knee OA were identified from the literature search, including six opinion-based, five evidence-based and 12 based on both expert opinion and research evidence. Twenty out of 51 treatment modalities addressed by these guidelines were universally recommended. ES for pain relief varied from treatment to treatment. Overall there was no statistically significant difference between non-pharmacological therapies [0.25, 95% confidence interval (CI) 0.16, 0.34] and pharmacological therapies (ES=0.39, 95% CI 0.31, 0.47). Following feedback from Osteoarthritis Research International members on the draft guidelines and six Delphi rounds consensus was reached on 25 carefully worded recommendations. Optimal management of patients with OA hip or knee requires a combination of non-pharmacological and pharmacological modalities of therapy. Recommendations cover the use of 12 non-pharmacological modalities: education and self-management, regular telephone contact, referral to a physical therapist, aerobic, muscle strengthening and water-based exercises, weight reduction, walking aids, knee braces, footwear and insoles, thermal modalities, transcutaneous electrical nerve stimulation and acupuncture. Eight recommendations cover pharmacological modalities of treatment including acetaminophen, cyclooxygenase-2 (COX-2) non-selective and selective oral non-steroidal anti-inflammatory drugs (NSAIDs), topical NSAIDs and capsaicin, intra-articular injections of corticosteroids and hyaluronates, glucosamine and/or chondroitin sulphate for symptom relief; glucosamine sulphate, chondroitin sulphate and diacerein for possible structure-modifying effects and the use of opioid analgesics for the treatment of refractory pain. There are recommendations covering five surgical modalities: total joint replacements, unicompartmental knee replacement, osteotomy and joint preserving surgical procedures; joint lavage and arthroscopic debridement in knee OA, and joint fusion as a salvage procedure when joint replacement had failed. Strengths of recommendation and 95% CIs are provided. Twenty-five carefully worded recommendations have been generated based on a critical appraisal of existing guidelines, a systematic review of research evidence and the consensus opinions of an international, multidisciplinary group of experts. The recommendations may be adapted for use in different countries or regions according to the availability of treatment modalities and SOR for each modality of therapy. These recommendations will be revised regularly following systematic review of new research evidence as this becomes available.
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            Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study.

            First-generation autologous chondrocyte implantation has limitations, and introducing new effective cell sources can improve cartilage repair. This study was conducted to compare the clinical outcomes of patients treated with first-generation autologous chondrocyte implantation to patients treated with autologous bone marrow-derived mesenchymal stem cells (BMSCs). Cohort study; Level of evidence, 3. Seventy-two matched (lesion site and age) patients underwent cartilage repair using chondrocytes (n = 36) or BMSCs (n = 36). Clinical outcomes were measured before operation and 3, 6, 9, 12, 18, and 24 months after operation using the International Cartilage Repair Society (ICRS) Cartilage Injury Evaluation Package, which included questions from the Short-Form Health Survey, International Knee Documentation Committee (IKDC) subjective knee evaluation form, Lysholm knee scale, and Tegner activity level scale. There was significant improvement in the patients' quality of life (physical and mental components of the Short Form-36 questionnaire included in the ICRS package) after cartilage repair in both groups (autologous chondrocyte implantation and BMSCs). However, there was no difference between the BMSC and the autologous chondrocyte implantation group in terms of clinical outcomes except for Physical Role Functioning, with a greater improvement over time in the BMSC group (P = .044 for interaction effect). The IKDC subjective knee evaluation (P = .861), Lysholm (P = .627), and Tegner (P = .200) scores did not show any significant difference between groups over time. However, in general, men showed significantly better improvements than women. Patients younger than 45 years of age scored significantly better than patients older than 45 years in the autologous chondrocyte implantation group, but age did not make a difference in outcomes in the BMSC group. Using BMSCs in cartilage repair is as effective as chondrocytes for articular cartilage repair. In addition, it required 1 less knee surgery, reduced costs, and minimized donor-site morbidity.
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              Donor age and cell passage affects differentiation potential of murine bone marrow-derived stem cells

              Background Bone marrow-derived mesenchymal stem cells (BMSCs) are a widely researched adult stem cell population capable of differentiation into various lineages. Because many promising applications of tissue engineering require cell expansion following harvest and involve the treatment of diseases and conditions found in an aging population, the effect of donor age and ex vivo handling must be understood in order to develop clinical techniques and therapeutics based on these cells. Furthermore, there currently exists little understanding as to how these two factors may be influenced by one another. Results Differences in the adipogenic, chondrogenic, and osteogenic differentiation capacity of murine MSCs harvested from donor animals of different age and number of passages of these cells were observed. Cells from younger donors adhered to tissue culture polystyrene better and proliferated in greater number than those from older animals. Chondrogenic and osteogenic potential decreased with age for each group, and adipogenic differentiation decreased only in cells from the oldest donors. Significant decreases in differentiation potentials due to passage were observed as well for osteogenesis of BMSCs from the youngest donors and chondrogenesis of the cells from the oldest donors. Conclusion Both increasing age and the number of passages have lineage dependent effects on BMSC differentiation potential. Furthermore, there is an obvious interplay between donor age and cell passage that in the future must be accounted for when developing cell-based therapies for clinical use.
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                Author and article information

                Contributors
                zhaoxinxinecnu@163.com
                yuanzhubiruan@sina.com
                tansentang@126.com
                leejiasjtu@163.com
                yingxuan.shi@cellbiomedgroup.com
                meng.li@cellbiomedgroup.com
                maggie.li@cellbiomedgroup.com
                cuili.xu@cellbiomedgroup.com
                + 86 (21)68383230 , drluqingsjtu@163.com
                + 86 (21)54069990 , chase.dai@cellbiomedgroup.com
                Journal
                Stem Cell Res Ther
                Stem Cell Res Ther
                Stem Cell Research & Therapy
                BioMed Central (London )
                1757-6512
                21 October 2019
                21 October 2019
                2019
                : 10
                : 308
                Affiliations
                [1 ]ISNI 0000 0004 0368 8293, GRID grid.16821.3c, Department of Radiology, Ren Ji Hospital, School of Medicine, , Shanghai Jiao Tong University, ; No. 160, Pujian Road, Shanghai, 200127 China
                [2 ]ISNI 0000 0004 0368 8293, GRID grid.16821.3c, Department of Rheumatology, Ren Ji Hospital, School of Medicine, , Shanghai Jiao Tong University, ; No. 160, Pujian Road, Shanghai, 200127 China
                [3 ]Cellular Biomedicine Group, Inc., No. 85 Faladi Road, Building 3, Zhangjiang, Pudong New Area, Shanghai, 201210 China
                Article
                1406
                10.1186/s13287-019-1406-7
                6805685
                31639063
                822acd5c-e441-492f-98df-32723482716f
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 5 May 2019
                : 21 August 2019
                : 3 September 2019
                Funding
                Funded by: National Key Research and Development Program of China
                Award ID: 2017YFC1103900
                Award ID: 2018YFB1105600
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81102267
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Molecular medicine
                multi-compositional mri sequences,knee osteoarthritis,composition alternations,repair cartilage,human adipose-derived mesenchymal progenitor cells

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