Clinical evaluation of micro-fragmented adipose tissue as a treatment option for patients with meniscus tears with osteoarthritis: a prospective pilot study

Gerard A Malanga, Paul S Chirichella, Nathan S Hogaboom, Teresa Capella, Gerard A Malanga, Paul S Chirichella, Nathan S Hogaboom, Teresa Capella

Abstract

Purpose: The management of knee pain secondary to meniscal tears with osteoarthritis is limited by the poor inherent healing potential of the meniscus. Previous studies have reported on the benefit of autologous micro-fragmented fat as a therapeutic for various knee pathologies. The goal of this prospective pilot study was to determine the safety and potential treatment effect of micro-fragmented adipose tissue injection for patients with knee pain secondary to osteoarthritis and meniscal tears who have failed conservative management.

Methods: Twenty subjects with knee pain secondary to osteoarthritis with associated meniscal tear after failed conservative management were enrolled in the study. Numeric Pain Scale (NPS) and Knee Injury and Osteoarthritis Outcome Scale (KOOS) following ultrasound-guided intra-meniscal and intra-articular micro-fragmented adipose tissue injections were examined at three, six and 12 months.

Results: The mean NPS revealed a significant decrease in patient pain at the 1-year time point compared with baseline (5.45 to 2.21, p < .001). Similarly, overall, mean KOOS symptoms significantly improved from 57.7 to 78.2 (p < .001), with all 4 KOOS subscales demonstrating significant improvement at the final one year follow-up. One subject developed uncomplicated cellulitis at the harvest site which was treated with oral antibiotics. Other complications were minor and mostly limited to adipose harvest.

Conclusion: This study demonstrated that micro-fragmented adipose tissue injected directly into a torn meniscus and knee joint using ultrasound guidance represents a safe and potentially efficacious treatment option for patients with knee pain suffering from degenerative arthritis and degenerative meniscal tears. A larger, randomized, controlled trial is warranted to determine efficacy.

Trial registration: Clinicaltrials.org Identifier: NCT03714659.

Keywords: Adipose tissue; Injections; Intra-articular; Knee injuries; Knee osteoarthritis; Meniscus; Ultrasonography.

Figures

Fig. 1
Fig. 1
Changes in Knee Injury and Osteoarthritis Outcome Score (KOOS) subscale scores in response to treatment. Increases were seen across all five subscales, which leveled off after 6 months through to 12 months post-treatment. Triangle = symptoms subscale, circle = pain subscale, square = activities of daily living subscale, diamond = sports and recreation subscale, “X” = quality of life subscale
Fig. 2
Fig. 2
Overall changes in numerical pain scale scores over the duration of the study. Decreases were observed at all time points were observed relative to pre-treatment pain levels. Improvements in pain appeared to level and remain steady after 6 months
Fig. 3
Fig. 3
Needle tip visualized in an out-of-plane view for MFAT injection into the meniscus under ultrasound guidance

References

    1. Fox AJS, Wanivenhaus F, Burge AJ, Warren RF, Rodeo SA. The human meniscus: a review of anatomy, function, injury, and advances in treatment. Clin Anat N Y N. 2015;28:269–287. doi: 10.1002/ca.22456.
    1. Miller R, Azar F (2017) Knee injuries. In: Campbell’s operative orthopaedics, 13th edn, Philadelphia, pp 2121–2297
    1. Badlani JT, Borrero C, Golla S, Harner CD, Irrgang JJ. The effects of meniscus injury on the development of knee osteoarthritis: data from the osteoarthritis initiative. Am J Sports Med. 2013;41:1238–1244. doi: 10.1177/0363546513490276.
    1. Tsujii A, Amano H, Tanaka Y, Kita K, Uchida R, Shiozaki Y, Horibe S. Second look arthroscopic evaluation of repaired radial/oblique tears of the midbody of the lateral meniscus in stable knees. J Orthop Sci. 2018;23:122–126. doi: 10.1016/j.jos.2017.09.023.
    1. Siemieniuk RAC, Harris IA, Agoritsas T, Poolman RW, Brignardello-Petersen R, Van de Velde S, Buchbinder R, Englund M, Lytvyn L, Quinlan C, Helsingen L, Knutsen G, Olsen NR, Macdonald H, Hailey L, Wilson HM, Lydiatt A, Kristiansen A. Arthroscopic surgery for degenerative knee arthritis and meniscal tears: a clinical practice guideline. BMJ. 2017;357:j1982. doi: 10.1136/bmj.j1982.
    1. Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98:1076–1084. doi: 10.1002/jcb.20886.
    1. Pak J, Lee JH, Lee SH (2014) Regenerative repair of damaged meniscus with autologous adipose tissue-derived stem cells. BioMed Res Int 2014(436029). 10.1155/2014/436029
    1. Pak J, Lee JH, Park KS, Jeon JH, Lee SH. Potential use of mesenchymal stem cells in human meniscal repair: current insights. Open Access J Sports Med. 2017;8:33–38. doi: 10.2147/OAJSM.S113018.
    1. Coleman SR. Structural fat grafting: more than a permanent filler. Plast Reconstr Surg. 2006;118:108S–120S. doi: 10.1097/01.prs.0000234610.81672.e7.
    1. 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. doi: 10.1007/s40778-016-0053-5.
    1. Bianchi F, Maioli M, Leonardi E, Olivi E, Pasquinelli G, Valente S, Mendez AJ, Ricordi C, Raffaini M, Tremolada C, Ventura C. A new nonenzymatic method and device to obtain a fat tissue derivative highly enriched in pericyte-like elements by mild mechanical forces from human lipoaspirates. Cell Transplant. 2013;22:2063–2077. doi: 10.3727/096368912X657855.
    1. Striano RD, Battista V, Bilboo N. Non-responding knee pain with osteoarthritis, meniscus and ligament tears treated with ultrasound guided autologous, micro-fragmented and minimally manipulated adipose tissue. Open J Regen Med. 2017;6:17–26. doi: 10.4236/ojrm.2017.62002.
    1. Ferreira-Valente MA, Pais-Ribeiro JL, Jensen MP. Validity of four pain intensity rating scales. Pain. 2011;152:2399–2404. doi: 10.1016/j.pain.2011.07.005.
    1. Tubach F, Ravaud P, Baron G, Falissard B, Logeart I, Bellamy N, Bombardier C, Felson D, Hochberg M, van der Heijde D, Dougados M (2005) Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement. Ann Rheum Dis 64:29–33 . 10.1136/ard.2004.022905
    1. Collins NJ, Misra D, Felson DT, Crossley KM, Roos EM. 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. 2011;63(Suppl 11):S208–S228. doi: 10.1002/acr.20632.
    1. Alviar MJ, Olver J, Brand C, Hale T, Khan F. Do patient-reported outcome measures used in assessing outcomes in rehabilitation after hip and knee arthroplasty capture issues relevant to patients? Results of a systematic review and ICF linking process. J Rehabil Med. 2011;43:374–381. doi: 10.2340/16501977-0801.
    1. Roos EM, Lohmander LS. The knee injury and osteoarthritis outcome score (KOOS): from joint injury to osteoarthritis. Health Qual Life Outcomes. 2003;1:64. doi: 10.1186/1477-7525-1-64.
    1. Baria MR, Sellon JL, Lueders D, Smith J. Sonographically guided knee meniscus injections: feasibility, techniques, and validation. PM&R. 2017;9:998–1005. doi: 10.1016/j.pmrj.2016.12.012.
    1. Lindstrom ML, Bates DM. Nonlinear mixed effects models for repeated measures data. Biometrics. 1990;46:673–687. doi: 10.2307/2532087.
    1. Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am. 2007;89:780–785. doi: 10.2106/JBJS.F.00222.
    1. Oberbauer E, Steffenhagen C, Wurzer C, Gabriel C, Redl H, Wolbank S (2015) Enzymatic and non-enzymatic isolation systems for adipose tissue-derived cells: current state of the art. Cell Regen Lond Engl:4:7. 10.1186/s13619-015-0020-0
    1. Vezzani B, Shaw I, Lesme H, Yong L, Khan N, Tremolada C, Péault B. Higher pericyte content and secretory activity of microfragmented human adipose tissue compared to enzymatically derived stromal vascular fraction. Stem Cells Transl Med. 2018;7:876–886. doi: 10.1002/sctm.18-0051.
    1. Lysaght T, Campbell AV. Regulating autologous adult stem cells: the FDA steps up. Cell Stem Cell. 2011;9:393–396. doi: 10.1016/j.stem.2011.09.013.
    1. Schroeder A, Rubin JP, Kokai L, Sowa G, Chen J, Onishi K Use of adipose-derived orthobiologics for musculoskeletal injuries: a narrative review. PM&R n/a. 10.1002/pmrj.12291
    1. De Decker M, De Schrijver L, Thiessen F, Tondu T, Van Goethem M, Tjalma WA. Breast cancer and fat grafting: efficacy, safety and complications-a systematic review. Eur J Obstet Gynecol Reprod Biol. 2016;207:100–108. doi: 10.1016/j.ejogrb.2016.10.032.
    1. Barret JP, Sarobe N, Grande N, Vila D, Palacin JM. Maximizing results for lipofilling in facial reconstruction. Clin Plast Surg. 2009;36:487–492. doi: 10.1016/j.cps.2009.02.005.
    1. Strong AL, Cederna PS, Rubin JP, Coleman SR, Levi B. The current state of fat grafting: a review of harvesting, processing, and injection techniques. Plast Reconstr Surg. 2015;136:897–912. doi: 10.1097/PRS.0000000000001590.
    1. Metcalf KB, Mandelbaum BR, McIlwraith CW. Application of platelet-rich plasma to disorders of the knee joint. Cartilage. 2013;4:295–312. doi: 10.1177/1947603513487553.
    1. Wei L-C, Gao S-G, Xu M, Jiang W, Tian J, Lei G-H. A novel hypothesis: the application of platelet-rich plasma can promote the clinical healing of white-white meniscal tears. Med Sci Monit Int Med J Exp Clin Res. 2012;18:HY47-50. doi: 10.12659/msm.883254.
    1. Ruiz Ibán MÁ, Comellas Melero N, Martinez-Botas J, Ortiz A, Diaz Heredia J. Growth factor expression after lesion creation in the avascular zone of the meniscus: a quantitative PCR study in rabbits. Arthrosc J Arthrosc Relat Surg. 2014;30:1131–1138. doi: 10.1016/j.arthro.2014.04.089.
    1. Tumia NS, Johnstone AJ. Platelet derived growth factor-AB enhances knee meniscal cell activity in vitro. Knee. 2009;16:73–76. doi: 10.1016/j.knee.2008.08.008.
    1. Guenoun D, Magalon J, de Torquemada I, Vandeville C, Sabatier F, Champsaur P, Jacquet C, Ollivier M. Treatment of degenerative meniscal tear with intrameniscal injection of platelets rich plasma. Diagn Interv Imaging. 2020;101:169–176. doi: 10.1016/j.diii.2019.10.003.
    1. Blanke F, Vavken P, Haenle M, von Wehren L, Pagenstert G, Majewski M. Percutaneous injections of Platelet rich plasma for treatment of intrasubstance meniscal lesions. Muscles Ligaments Tendons J. 2015;5:162–166. doi: 10.11138/mltj/2015.5.3.162.
    1. Kaminski R, Maksymowicz-Wleklik M, Kulinski K, Kozar-Kaminska K, Dabrowska-Thing A, Pomianowski S (2019) Short-term outcomes of percutaneous trephination with a platelet rich plasma intrameniscal injection for the repair of degenerative meniscal lesions. A prospective, randomized, double-blind, parallel-group, placebo-controlled study. Int J Mol Sci 20. 10.3390/ijms20040856
    1. Striano RD, Chen H, Bilbool N, Azatullah K, Hilado J, Horan K Non-responsive knee pain with osteoarthritis and concurrent meniscal disease treated with autologous micro-fragmented adipose tissue under continuous ultrasound guidance. 7
    1. Katz JN, Brophy RH, Chaisson CE, de Chaves L, Cole BJ, Dahm DL, Donnell-Fink LA, Guermazi A, Haas AK, Jones MH, Levy BA, Mandl LA, Martin SD, Marx RG, Miniaci A, Matava MJ, Palmisano J, Reinke EK, Richardson BE, Rome BN, Safran-Norton CE, Skoniecki DJ, Solomon DH, Smith MV, Spindler KP, Stuart MJ, Wright J, Wright RW, Losina E. Surgery versus physical therapy for a meniscal tear and osteoarthritis. N Engl J Med. 2013;368:1675–1684. doi: 10.1056/NEJMoa1301408.
    1. Bowers ME, Tung GA, Fleming BC, Crisco JJ, Rey J. Quantification of meniscal volume by segmentation of 3T magnetic resonance images. J Biomech. 2007;40:2811–2815. doi: 10.1016/j.jbiomech.2007.01.016.
    1. Vangsness CT, Farr J, Boyd J, Dellaero DT, Mills CR, LeRoux-Williams M. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. J Bone Joint Surg Am. 2014;96:90–98. doi: 10.2106/JBJS.M.00058.
    1. Saltzman BM, Leroux T, Meyer MA, Basques BA, Chahal J, Bach BR, Yanke AB, Cole BJ. 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. doi: 10.1177/0363546516680607.

Source: PubMed

3
Abonnieren