Patient-Centered Outcomes of Microfragmented Adipose Tissue Treatments of Knee Osteoarthritis: An Observational, Intention-to-Treat Study at Twelve Months
TL;DR: A positive role for intra-articular injection of MFAT as a treatment for knee osteoarthritis is suggested and statistically significant improvements in pain, function, and quality of life were reported.
Abstract: Introduction. Microfragmented adipose tissue (MFAT) has been shown to benefit osteoarthritic patients by reducing pain and supporting tissue regeneration through a mesenchymal stem cell (MSC)-related paracrine mechanism. This observational study of 110 knees assessed patient-centered outcomes of pain, functionality, and quality of life, analyzing their variation at twelve months following one ultrasound-guided intra-articular injection of autologous MFAT for the treatment of knee osteoarthritis (KOA). Method. Inclusion criteria were as follows: VAS >50, and the presence of KOA as diagnosed on X-ray and MRI. Exclusion criteria included the following: recent injury ( ); median OKS (function) improved from 25 (IQR 11) to 33.5 (IQR 16) ( ); and median EQ-5D (quality of life) improved from 0.62 (IQR 0.41) to 0.69 (IQR 0.28) ( ). No adverse events were reported during the intraoperative, recovery, or postoperative periods. Conclusions. For patients with all grades of knee osteoarthritis who were treated with intra-articular injections of MFAT, statistically significant improvements in pain, function, and quality of life were reported. Although further research is warranted, the results are encouraging and suggest a positive role for intra-articular injection of MFAT as a treatment for knee osteoarthritis.
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TL;DR: In this article, the authors evaluated the short-term clinical effect, therapeutic response rate (TRR), and therapy safety of a single intra-articular autologous MFAT injection for symptomatic knee OA.
Abstract: The study aimed to evaluate the short-term clinical effect, therapeutic response rate (TRR%), and therapy safety of a single intra-articular autologous MFAT injection for symptomatic knee OA. Secondly, patient- and pathology-related parameters were investigated to tighten patient selection for MFAT therapy. Sixty-four subjects with symptomatic mild–severe knee OA were enrolled in a single-center trial and received a unilateral (n = 37) or bilateral (n = 27) MFAT injection. After liposuction, the adipose tissue was mechanically processed with the Lipogem® device, which eventually produced 8–10 cc of MFAT. Subjects were clinically assessed by means of the KOOS, NRS, UCLA, and EQ-5D at baseline and 1, 3, 6, and 12 months after injection. Adverse events were recorded at each follow-up timepoint. The TRR was defined according to the OMERACT-OARSI criteria and baseline MRI was scored following the MOAKS classification. The TRR of the index knee was 64% at 3 months and 45% at 12 months after injection. Therapy responders at 12 months improved with 28.3 ± 11.4 on KOOS pain, while non-responders lost −2.1 ± 11.2 points. All clinical scores, except the UCLA, improved significantly at follow-up compared to baseline (p < 0.05). In the bilateral cohort, no difference in baseline scores or TRR was found between the index knee and contralateral knee (n.s.). An inflammatory reaction was reported in 79% of knees and resolved spontaneously within 16.6 ± 13.5 days after MFAT administration. Numerous bone marrow lesions (BML) were negatively correlated with the TRR at 12 months (p = 0.003). The study demonstrated an early clinical improvement but a mediocre response rate of 45% at 12 months after a single intra-articular injection with autologous MFAT. Assessment of bone marrow lesions on MRI can be helpful to increase the therapeutic responsiveness of MFAT up to 70% at 12 months. In comparison to repetitive injection therapies such as cortisone, hyaluronic acid, and PRP, administration of MFAT might become a relevant alternative in well-selected patients with symptomatic knee OA.
9 citations
TL;DR: In this article, a microfragmented adipose tissue (MFAT) injection was used to relieve pain and improve function in knee osteoarthritis patients with Kellgren-Lawrence grade 3 and 4.
Abstract: Background Knee osteoarthritis (KOA) is a significant cause of disability in a globally ageing population. Knee replacement surgery has been shown to improve function and quality of life. Access to this intervention can be limited for a number of reasons including rationing of care, lack of healthcare provision in austere environments, and more recently, due to the cessation of elective orthopaedic care as a result of the COVID pandemic. Referral for knee replacement surgery is often guided by the patient's Oxford Knee Score (OKS). Recent therapies including treatment with microfragmented adipose tissue (MFAT) have emerged as alternatives to relieve pain and improve function in such patients. Method We identified all patients with KOA Kellgren-Lawrence grade 3 and 4 in our dataset of patients treated with a single injection of MFAT and applied published OKS thresholds for referral for TKR to separate them into 3 cohorts according to their functional impairment. 220 patients (95 females, 125 males) with KOA were given one MFAT injection. The function (OKS) and quality of life (EuroQol-5) prior to and 24 months after therapy were compared. Results MFAT injection provided a statistically significant improvement in the quality of life (EQ-5D) at 24 months in patients with a baseline OKS of 39 or less (p value: <0.001) as well as those with OKS of 27 or less who are deemed suitable for a knee replacement (p value: <0.001). Conclusion MFAT injection improves quality of life in patients with KOA who are deemed suitable for the knee replacement. MFAT is a low-morbidity alternative biological treatment and can delay the need for total knee replacement in suitable patients.
8 citations
TL;DR: The collected clinical results suggest that MFAT may represent a safe and effective treatment for OA symptoms, offering a low-demanding and minimally invasive treatment.
Abstract: The purpose of the present study was to assess, prospectively, the safety, clinical effectiveness, and feasibility of a single intra-articular injection of microfragmented adipose tissue in different stages of knee osteoarthritis (OA). The study included patients (aged 18–70 years), affected by OA (Kellgren–Lawrence I-IV). Unselected patients were evaluated before and prospectively after 6, 12, and 24 months from the injection. Visual analog scale (VAS) and knee injury and osteoarthritis outcome score (KOOS) were used for clinical evaluations. A total of 202 patients were eligible. The mean follow-up time in the cohort of patients was 24.5 ± 9.6 months. Total KOOS significantly improved from pre-operative baseline levels to 6-month follow-up (p < 0.001), and again between 6- and 12-month follow-ups (p < 0.001). The VAS showed a prompt reduction at 6 months (p < 0.001 vs. baseline), but then it increased again at 12 months compared to the 6-month assessment (p < 0.001), even though it remained lower than baseline (p < 0.001). At 24 months, patients with KL-IV demonstrated a lower improvement compared to baseline; patients that had undergone previous corticosteroid injections had a greater risk to further injection treatment. The collected clinical results suggest that MFAT may represent a safe and effective treatment for OA symptoms, offering a low-demanding and minimally invasive treatment.
8 citations
TL;DR: In this article, a variation was found in the MFAT cluster size between individual samples and this translated into a similar variation in the ability of purified mesenchymal stem cells (MSCs) to form colony-forming units.
Abstract: Adipose tissue and more specifically micro-fragmented adipose tissue (MFAT) obtained from liposuction has recently been shown to possess interesting medicinal properties whereby its application supports pain reduction and may enhance tissue regeneration particularly in osteoarthritis. Here we have characterised samples of MFAT produced using the Lipogems® International Spa system from eight volunteer individuals in order to understand the critical biological mechanisms through which they act. A variation was found in the MFAT cluster size between individual samples and this translated into a similar variation in the ability of purified mesenchymal stem cells (MSCs) to form colony-forming units. Almost all of the isolated cells were CD105/CD90/CD45+ indicating stemness. An analysis of the secretions of cytokines from MFAT samples in a culture using targeted arrays and an enzyme-linked immunosorbent assay (ELISA) showed a long-term specific and significant expression of proteins associated with anti-inflammation (e.g., interleukin-1 receptor alpha (Il-1Rα) antagonist), pro-regeneration (e.g., hepatocyte growth factor), anti-scarring and pro-angiogenesis (e.g., transforming growth factor beta 1 and 2 (TGFβ1/2) and anti-bacterial (e.g., chemokine C-X-C motif ligand-9 (CXCL-9). Angiogenesis and angiogenic signalling were notably increased in primary bovine aortic endothelial cells (BAEC) to a different extent in each individual sample of the conditioned medium whilst a direct capacity of the conditioned medium to block inflammation induced by lipopolysaccharides was shown. This work characterises the biological mechanisms through which a strong, long-lasting, and potentially beneficial effect can be observed regarding pain reduction, protection and regeneration in osteoarthritic joints treated with MFAT.
7 citations
TL;DR: A single intra-articular injection of MF-AT was not superior to PRP, with comparable low numbers of failures and adverse events and without disease progression.
Abstract: Background: Intra-articular microfragmented adipose tissue (MF-AT) injections have been proposed for the treatment of knee osteoarthritis (OA). Purpose: To compare a single injection of MF-AT or platelet-rich plasma (PRP) in terms of clinical outcomes and OA progression. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 118 patients with symptomatic knee OA were randomized to receive a single intra-articular injection of MF-AT or PRP. Patients were evaluated before the injection and at 1, 3, 6, 12, and 24 months with the International Knee Documentation Committee (IKDC) subjective score, Knee injury and Osteoarthritis Outcome Score (KOOS) subscales, EuroQol visual analogue scale (EQ-VAS), EuroQol 5 dimensions (EQ-5D), and visual analogue scale (VAS) for pain. Primary outcomes were the IKDC subjective score and the KOOS pain subscore at 6 months. Knees were evaluated at baseline and at 6, 12, and 24 months with radiography and high-resolution magnetic resonance imaging (MRI) using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Results: Both MF-AT and PRP provided a statistically and clinically significant improvement up to 24 months. The improvement in the IKDC subjective score from baseline to 6 months was similar in both MF-AT (41.1 ± 16.3 to 57.3 ± 18.8) and PRP (44.8 ± 17.3 to 58.4 ± 18.1) groups (P < .0005). The improvement in the KOOS pain subscore from baseline to 6 months was similar in both the MF-AT (58.4 ± 15.9 to 75.8 ± 17.4) and PRP (63.5 ± 17.8 to 75.5 ± 16.1) groups (P < .0005). Overall, no differences were found between the MF-AT and PRP groups in terms of clinical outcomes, adverse events (18.9% and 10.9%, respectively), and failures (15.1% and 25.5%, respectively). Radiographic and MRI findings did not show changes after the injection. As a secondary outcome, more patients in the MF-AT group with moderate/severe OA reached the minimal clinically important difference for the IKDC score at 6 months compared with the PRP group (75.0% vs 34.6%, respectively; P = .005). Conclusion: A single intra-articular injection of MF-AT was not superior to PRP, with comparable low numbers of failures and adverse events and without disease progression. No differences were found in clinical and imaging results between the 2 biological approaches.
7 citations
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TL;DR: Adult stem cells isolated from marrow aspirates of volunteer donors could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages.
Abstract: Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.
20,479 citations
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12,135 citations
Royal North Shore Hospital1, University of Queensland2, Charité3, University of Melbourne4, University of Sydney5, University of Western Sydney6, University of Lorraine7, University of Adelaide8, Menzies Research Institute9, Monash University10, Deakin University11, Institute for Health Metrics and Evaluation12, Royal Cornwall Hospital13
TL;DR: In this article, the global burden of hip and knee OA was estimated as part of the Global Burden of Disease 2010 study and the burden of OA compared with other conditions.
Abstract: Objective To estimate the global burden of hip and knee osteoarthritis (OA) as part of the Global Burden of Disease 2010 study and to explore how the burden of hip and knee OA compares with other conditions. Methods Systematic reviews were conducted to source age-specific and sex-specific epidemiological data for hip and knee OA prevalence, incidence and mortality risk. The prevalence and incidence of symptomatic, radiographic and self-reported hip or knee OA were included. Three levels of severity were defined to derive disability weights (DWs) and severity distribution (proportion with mild, moderate and severe OA). The prevalence by country and region was multiplied by the severity distribution and the appropriate disability weight to calculate years of life lived with disability (YLDs). As there are no deaths directly attributed to OA, YLDs equate disability-adjusted life years (DALYs). Results Globally, of the 291 conditions, hip and knee OA was ranked as the 11th highest contributor to global disability and 38th highest in DALYs. The global age-standardised prevalence of knee OA was 3.8% (95% uncertainty interval (UI) 3.6% to 4.1%) and hip OA was 0.85% (95% UI 0.74% to 1.02%), with no discernible change from 1990 to 2010. Prevalence was higher in females than males. YLDs for hip and knee OA increased from 10.5 million in 1990 (0.42% of total DALYs) to 17.1 million in 2010 (0.69% of total DALYs). Conclusions Hip and knee OA is one of the leading causes of global disability. Methodological issues within this study make it highly likely that the real burden of OA has been underestimated. With the aging and increasing obesity of the world9s population, health professions need to prepare for a large increase in the demand for health services to treat hip and knee OA.
2,440 citations
"Patient-Centered Outcomes of Microf..." refers background in this paper
...Given that arthritis is such a prevalent condition, especially among an ageing population [22], it is vital to identify the long-term efficacy of therapies that utilize the regenerative power of adipose-derived MSCs, and whether they can potentially prevent replacement surgery or delay it for as long as possible....
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TL;DR: In this article, a 12-item questionnaire for patients having a total knee replacement (TKR) was developed and a prospective study of 117 patients before operation and at follow-up six months later, asking them to complete the new questionnaire and the form SF36.
Abstract: We have developed a 12-item questionnaire for patients having a total knee replacement (TKR). We made a prospective study of 117 patients before operation and at follow-up six months later, asking them to complete the new questionnaire and the form SF36. Some also filled in the Stanford Health Assessment Questionnaire (HAQ). An orthopaedic surgeon completed the American Knee Society (AKS) clinical score. The single score derived from the new questionnaire had high internal consistency, and its reproducibility, examined by test-retest reliability, was found to be satisfactory. Its validity was established by obtaining significant correlations in the expected direction with the AKS scores and the relevant parts of the SF36 and HAQ. Sensitivity to change was assessed by analysing the differences between the preoperative scores and those at follow-up. We also compared change in scores with the patients' retrospective judgement of change in their condition. The effect size for the new questionnaire compared favourably with those for the relevant parts of the SF36. The change scores for the new knee questionnaire were significantly greater (p < 0.0001) for patients who reported the most improvement in their condition. The new questionnaire provides a measure of outcome for TKR that is short, practical, reliable, valid and sensitive to clinically important changes over time.
2,177 citations
TL;DR: Low-grade inflammation induced by the metabolic syndrome, innate immunity and inflammaging are some of the more recent arguments in favor of the inflammatory theory of OA and highlighted in this review.
1,225 citations
"Patient-Centered Outcomes of Microf..." refers background in this paper
...Furthermore, the cells are not adversely influenced by the age of the patient; a factor that is very beneficial for an elderly population [21]....
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