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      Autologous micro-fragmented adipose tissue injection provides significant and prolonged clinical improvement in patients with knee osteoarthritis: a case-series study

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          Abstract

          Purpose

          Among the conservative strategies to manage patients with symptomatic knee osteoarthritis (OA), an innovative approach exploiting the regenerative capability of adipose tissue and its resident MSCs (Mesenchymal Stem Cells or Medicinal Signalling Cells) has been proposed with encouraging results. This study aims to demonstrate the benefits of autologous micro-fragmented adipose tissue (MAT) injection in the conservative treatment of knee osteoarthritis and whether any variables may affect the outcome. This is a case series single-centre study in which patients underwent intraarticular MAT injection without any associated procedures.

          Methods

          Based on inclusion and exclusion criteria, 49 patients (67 Knees) were included and retrospectively analysed with a mean follow-up of 34.04 ± 13.62 months (minimum 11 – maximum 59). Patients were assessed through the WOMAC and KOOS questionnaires at baseline (pre-treatment) and 1-, 3-, 6-, 12-, 24- and 36-month follow-up. A minimal clinically important difference (MCID) of at least 7.5 points for the WOMAC pain scale and 7.2 for the WOMAC function scale compared to the baseline value was used.

          Results

          WOMAC and KOOS scores improved after treatment compared to baseline at all follow-ups with p < 0.001. Male gender and Kellgren-Lawrence (KL) grade 2 were associated with smaller improvement in WOMAC and KOOS scores (with respect to females and to KL grade 1, respectively) up to 24 months. The percentage of patients who reach the MCID for WOMAC pain is generally lower than that of patients who reach the MCID for WOMAC function (around 80% at all time points), but it increases significantly over time. Moreover, the baseline score of the WOMAC pain and function influence the outcome. Patients with worse symptoms are more likely to reach the MCID.

          Conclusions

          Intra-articular knee injection of MAT for the treatment of knee osteoarthritis (KOA), recalcitrant to traditional conservative treatments, proved to be effective in a high percentage of cases. The positive association between a worse pre-operative score and a better clinical response to the treatment would support the idea that intra-articular administration of MAT could be considered in patients with very symptomatic KOA in which joint-replacement surgeries are not indicated (or accepted).

          Level of Evidence

          IV, case series.

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          Most cited references50

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          OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis

          To update and expand upon prior Osteoarthritis Research Society International (OARSI) guidelines by developing patient-focused treatment recommendations for individuals with Knee, Hip, and Polyarticular osteoarthritis (OA) that are derived from expert consensus and based on objective review of high-quality meta-analytic data.
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            Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial.

            : Osteoarthritis (OA) is the most widespread musculoskeletal disorder in adults. It leads to cartilage damage associated with subchondral bone changes and synovial inflammation, causing pain and disability. The present study aimed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells (ASCs) in patients with knee OA, as well as clinical efficacy as secondary endpoint. A bicentric, uncontrolled, open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries. From April 2012 to December 2013, 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra-articular injection of autologous ASCs. The study design consisted of three consecutive cohorts (six patients each) with dose escalation: low dose (2 × 10(6) cells), medium dose (10 × 10(6)), and high dose (50 × 10(6)). The primary outcome parameter was safety evaluated by recording adverse events throughout the trial, and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index. After 6 months of follow-up, the procedure was found to be safe, and no serious adverse events were reported. Four patients experienced transient knee joint pain and swelling after local injection. Interestingly, patients treated with low-dose ASCs experienced significant improvements in pain levels and function compared with baseline. Our data suggest that the intra-articular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients. A placebo-controlled double-blind phase IIb study is being initiated to assess clinical and structural efficacy.
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              Nanofat grafting: basic research and clinical applications.

              The indications for fat grafting are increasing steadily. In microfat grafting, thin injection cannulas are used. The authors describe their experience of fat injection with even thinner injection needles up to 27 gauge. The fat used for this purpose is processed into "nanofat." Clinical applications are described. Preliminary results of a study, set up to determine the cellular contents of nanofat, are presented.
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                Author and article information

                Contributors
                arcangelorusso@yahoo.it
                Journal
                J Exp Orthop
                J Exp Orthop
                Journal of Experimental Orthopaedics
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                2197-1153
                16 November 2023
                16 November 2023
                December 2023
                : 10
                : 116
                Affiliations
                [1 ]Department of Orthopedics, Joint Prosthetic, Arthroscopic Surgery and Sports Traumatology, Humanitas Castelli, ( https://ror.org/02ma9m113) Via Mazzini 11, 24128 Bergamo, Italy
                [2 ]Department of Orthopaedic and Trauma Surgery, University Campus Bio-Medico of Rome, ( https://ror.org/04gqx4x78) 00128 Rome, Italy
                [3 ]Engineering Department, University of Bergamo, ( https://ror.org/02mbd5571) Viale Marconi, 5, 24044 Dalmine, BG Italy
                Author information
                http://orcid.org/0000-0003-4120-3333
                Article
                668
                10.1186/s40634-023-00668-y
                10651566
                37968496
                0823d8a0-2aa8-4e34-8c72-4dc045f45750
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 24 February 2023
                : 9 October 2023
                Categories
                Original Paper
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                © European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA) 2023

                micro-fragmented adipose tissue (mat),mesenchymal stem cells or medicinal signalling,cells (mscs),knee osteoarthritis (koa),minimal clinical important difference (mcid)

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