Advertisement

Intra-Articular Injection of Autologous Microfat and Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Double-Blind Randomized Comparative Study

      Purpose

      To compare a single abdominal microfat (MF) injection mixed or not with platelet-rich plasma (PRP) Low Dose (LD) or High Dose (HD) in order to improve MRI parameters, alleviate pain and enhance functional capacity in knee osteoarthritis.

      Methods

      Patients with symptomatic grade 2 to 4 knee osteoarthritis according to the International Cartilage Repair Society MRI classification were selected. They were prospectively assessed at baseline and at 3 and 6 months of follow-up. The primary endpoint was change in the maximum of value of cartilage relaxation time in T2 mapping sequences (T2max) at 3 months. Secondary endpoints were MRI grade severity and joint space assessment, Western Ontario and McMaster Universities Arthritis Index score, pain evaluation, knee range of motion, and patients’ satisfaction. Adverse events were also collected. The complete cell counts and growth factors content of injected products were assessed to analyze their potential relationship with MRI and clinical outcomes.

      Results

      Three groups of 10 patients received a single injection of 10 cc of a mix (1:1) containing MF-Saline, MF-PRP LD or MF-PRP HD. T2max did not change significantly over the time for any of the groups. All treatments significantly improved knee functional status and symptom relief at 3 and 6 months. All patients were responders in the MF/PRP HD at 3 months and significantly higher compared to MF/PRP LD. Half of the injected PRP in the MF/PRP LD group displayed red blood cell contamination of over 8%, which was correlated with an impairment of T2max.

      Conclusion

      A single intra-articular injection of MF with or without PRP is safe and may offer a significant clinical improvement in patients with osteoarthritis.

      Level of evidence

      2; randomized double-blind comparative parallel-group trial (RCT No.: NCT04352075).
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Arthroscopy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Global Burden of Disease 2017 Disease and Injury Incidence and Prevalence Collaborators
        Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017.
        Lancet. 2018; 392: 1789-1858
        • Vos T.
        • Flaxman A.D.
        • Naghavi M.
        • et al.
        Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010.
        Lancet. 2012; 380: 2163-2196https://doi.org/10.1016/S0140-6736(12)61729-2
        • Wallace I.J.
        • Worthington S.
        • Felson D.T.
        • et al.
        Knee osteoarthritis has doubled in prevalence since the mid-20th century.
        Proc Natl Acad Sci U S A. 2017; 114: 9332-9336
        • Hepper C.T.
        • Halvorson J.J.
        • Duncan S.T.
        • Gregory A.J.
        • Dunn W.R.
        • Spindler K.P.
        The efficacy and duration of intra-articular corticosteroid injection for knee osteoarthritis: A systematic review of level I studies.
        J Am Acad Orthop Surg. 2009; 17: 638-646
        • Kompel A.J.
        • Roemer F.W.
        • Murakami A.M.
        • Diaz L.E.
        • Crema M.D.
        • Guermazi A.
        Intra-articular corticosteroid injections in the hip and knee: perhaps not as safe as we thought?.
        Radiology. 2019; 293: 656-663
        • Zhang W.
        • Moskowitz R.W.
        • Nuki G.
        • et al.
        OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines.
        Osteoarthritis Cartilage. 2008; 16: 137-162
        • Marx R.E.
        Platelet-rich plasma (PRP): What is PRP and what is not PRP?.
        Implant Dent. 2001; 10: 225-228
        • Dhillon M.S.
        • Patel S.
        • John R.
        PRP in OA knee: Update, current confusions and future options.
        Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT) J. 2017; 3: 27
        • Sundman E.A.
        • Cole B.J.
        • Fortier L.A.
        Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma.
        Am J Sports Med. 2011; 39: 2135-2140
        • Dai W.L.
        • Zhou A.G.
        • Zhang H.
        • Zhang J.
        Efficacy of platelet-rich plasma in the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials.
        Arthroscopy. 2017; 33: 659-670
        • Buendía-López D.
        • Medina-Quirós M.
        • Fernández-Villacañas Marín M.Á.
        Clinical and radiographic comparison of a single LP-PRP injection, a single hyaluronic acid injection and daily NSAID administration with a 52-week follow-up: A randomized controlled trial.
        J Orthop Traumatol. 2018; 19: 3
        • Guillibert C.
        • Charpin C.
        • Raffray M.
        • et al.
        Single injection of high volume of autologous pure PRP provides a significant improvement in knee osteoarthritis: A prospective routine care study.
        Int J Mol Sci. 2019; 20: 1327
        • Maumus M.
        • Manferdini C.
        • Toupet K.
        • et al.
        Adipose mesenchymal stem cells protect chondrocytes from degeneration associated with osteoarthritis.
        Stem Cell Res. 2013; 11: 834-844
        • Zuk P.A.
        • Zhu M.
        • Mizuno H.
        • et al.
        Multilineage cells from human adipose tissue: Implications for cell-based therapies.
        Tissue Eng. 2001; 7: 211-228
        • Nguyen P.S.
        • Desouches C.
        • Gay A.M.
        • Hautier A.
        • Magalon G.
        Development of micro-injection as an innovative autologous fat graft technique: The use of adipose tissue as dermal filler.
        J Plast Reconstr Aesthet Surg. 2012; 65: 1692-1699
        • Eto H.
        • Kato H.
        • Suga H.
        • et al.
        The fate of adipocytes after nonvascularized fat grafting: Evidence of early death and replacement of adipocytes.
        Plast Reconstr Surg. 2012; 129: 1081-1092
        • Alharbi Z.
        • Opländer C.
        • Almakadi S.
        • Fritz A.
        • Vogt M.
        • Pallua N.
        Conventional vs. micro-fat harvesting: How fat harvesting technique affects tissue-engineering approaches using adipose tissue-derived stem/stromal cells.
        J Plast Reconstr Aesthet Surg. 2013; 66: 1271-1278
        • Bosetti M.
        • Borrone A.
        • Follenzi A.
        • Messaggio F.
        • Tremolada C.
        • Cannas M.
        Human lipoaspirate as autologous injectable active scaffold for one-step repair of cartilage defects.
        Cell Transplant. 2016; 25: 1043-1056
        • Mayoly A.
        • Iniesta A.
        • Curvale C.
        • et al.
        Development of autologous platelet-rich plasma mixed-microfat as an advanced therapy medicinal product for intra-articular injection of radio-carpal osteoarthritis: From validation data to preliminary clinical results.
        Int J Mol Sci. 2019; 20: 1111
        • Sautereau N.
        • Daumas A.
        • Truillet R.
        • et al.
        Efficacy of autologous microfat graft on facial handicap in systemic sclerosis patients.
        Plast Reconstr Surg Glob Open. 2016; 4e660
        • Graiet H.
        • Lokchine A.
        • Francois P.
        • et al.
        Use of platelet-rich plasma in regenerative medicine: Technical tools for correct quality control.
        BMJ Open Sport Exerc Med. 2018; 4e000442
        • Bellamy N.
        • Buchanan W.W.
        • Goldsmith C.H.
        • Campbell J.
        • Stitt L.W.
        Validation study of WOMAC: A health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee.
        J Rheumatol. 1988; 15: 1833-1840
        • Collins N.J.
        • Misra D.
        • Felson D.T.
        • Crossley K.M.
        • Roos E.M.
        Measures of knee function: International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form, Knee Injury and Osteoarthritis Outcome Score (KOOS), Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS), Knee Outcome Survey Activities of Daily Living Scale (KOS-ADL), Lysholm Knee Scoring Scale, Oxford Knee Score (OKS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Activity Rating Scale (ARS), and Tegner Activity Score (TAS).
        Arthritis Care Res (Hoboken). 2011; 63: S208-S228
        • Clement N.D.
        • Bardgett M.
        • Weir D.
        • Holland J.
        • Gerrand C.
        • Deehan D.J.
        What is the minimum clinically important difference for the WOMAC Index After TKA?.
        Clin Orthop Relat Res. 2018; 476: 2005-2014
        • Cağlar E.
        • Şahin G.
        • Oğur T.
        • Aktaş E.
        Quantitative evaluation of hyaline articular cartilage T2 maps of knee and determine the relationship of cartilage T2 values with age, gender, articular changes.
        Eur Rev Med Pharmacol Sci. 2014; 18: 3386-3393
        • Louis M.L.
        • Magalon J.
        • Jouve E.
        • et al.
        Growth factors levels determine efficacy of platelets rich plasma injection in knee osteoarthritis: A randomized double blind noninferiority trial compared with viscosupplementation.
        Arthroscopy. 2018; 34: 1530-1540.e2
        • Zhang W.
        • Robertson J.
        • Jones A.C.
        • Dieppe P.A.
        • Doherty M.
        The placebo effect and its determinants in osteoarthritis: Meta-analysis of randomised controlled trials.
        Ann Rheum Dis. 2008; 67: 1716-1723
        • Saltzman B.M.
        • Leroux T.
        • Meyer M.A.
        • et al.
        The therapeutic effect of intra-articular normal saline injections for knee osteoarthritis: A Meta-analysis of Evidence Level 1 Studies.
        Am J Sports Med. 2017; 45: 2647-2653
        • Zhu M.
        • Cohen S.R.
        • Hicok K.C.
        • et al.
        Comparison of three different fat graft preparation methods: Gravity separation, centrifugation, and simultaneous washing with filtration in a closed system.
        Plast Reconstr Surg. 2013; 131: 873-880
        • Hudetz D.
        • Borić I.
        • Rod E.
        • et al.
        The effect of intra-articular injection of autologous microfragmented fat tissue on proteoglycan synthesis in patients with knee osteoarthritis.
        Genes (Basel). 2017; 8: 270
        • Borić I.
        • Hudetz D.
        • Rod E.
        • et al.
        A 24-month follow-up study of the effect of intra-articular injection of autologous microfragmented fat tissue on proteoglycan synthesis in patients with knee osteoarthritis.
        Genes (Basel). 2019; 10: 1051
        • Pintat J.
        • Silvestre A.
        • Magalon G.
        • et al.
        Intra-articular injection of mesenchymal stem cells and platelet-rich plasma to treat patellofemoral osteoarthritis: Preliminary results of a long-term pilot study.
        J Vasc Interv Radiol. 2017; 28: 1708-1713
        • Casula V.
        • Hirvasniemi J.
        • Lehenkari P.
        • et al.
        Association between quantitative MRI and ICRS arthroscopic grading of articular cartilage.
        Knee Surg Sports Traumatol Arthrosc. 2016; 24: 2046-2054
        • Lansdown D.A.
        • Wang K.
        • Cotter E.
        • Davey A.
        • Cole B.J.
        Relationship between quantitative MRI biomarkers and patient-reported outcome measures after cartilage repair surgery: A systematic review.
        Orthop J Sports Med. 2018; 6 (2325967118765448)
        • Goebel J.C.
        • Watrin-Pinzano A.
        • Bettembourg-Brault I.
        • et al.
        Age-related quantitative MRI changes in healthy cartilage: Preliminary results.
        Biorheology. 2006; 434: 547-551
        • Eckstein F.
        • Burstein D.
        • Link T.M.
        Quantitative MRI of cartilage and bone: Degenerative changes in osteoarthritis.
        NMR Biomed. 2006; 19: 822-854
        • Braun H.J.
        • Kim H.J.
        • Chu C.R.
        • Dragoo J.L.
        The effect of platelet-rich plasma formulations and blood products on human synoviocytes: Implications for intra-articular injury and therapy.
        Am J Sports Med. 2014; 42: 1204-1210
        • Everts P.A.
        • Malanga G.A.
        • Paul R.V.
        • Rothenberg J.B.
        • Stephens N.
        • Mautner K.R.
        Assessing clinical implications and perspectives of the pathophysiological effects of erythrocytes and plasma-free hemoglobin in autologous biologics for use in musculoskeletal regenerative medicine therapies: A review.
        Regen Ther. 2019; 11: 56-64
        • Chu C.R.
        • Rodeo S.
        • Bhutani N.
        • et al.
        Optimizing clinical use of biologics in orthopaedic surgery: Consensus recommendations from the 2018 AAOS/NIH U-13 Conference.
        J Am Acad Orthop Surg. 2019; 27: e50-e63
        • Jorgensen C.
        • Djouad F.
        • Bouffi C.
        • Mrugala D.
        • Noël D.
        Multipotent mesenchymal stromal cells in articular diseases.
        Best Pract Res Clin Rheumatol. 2008; 22: 269-284
        • Tremolada C.
        • Colombo V.
        • Ventura C.
        Adipose tissue and mesenchymal stem cells: State of the art and lipogems technology development.
        Curr Stem Cell Rep. 2016; 2: 304-312
        • Nava S.
        • Sordi V.
        • Pascucci L.
        • et al.
        Long-lasting anti-inflammatory activity of human microfragmented adipose tissue.
        Stem Cells Int. 2019; : 5901479