Abstract
Purpose
The purpose of the present study was to investigate the mid-term outcomes of a single-stage cell-based procedure in patients with knee focal symptomatic cartilage defects using matrix-induced culture-expanded autologous AD-MSCs. It was hypothesised that the increased number of autologous AD-MSCs after culture expansion is a safe and efficient cartilage repair procedure, which improves overtime chondrogenesis in cartilage lesions
Methods
Twenty-five consecutive patients treated for a symptomatic cartilage defect were prospectively followed for 3 years. The median age of patients was 30.5 (range 16–43) with a median BMI of 23.6 kg/m2 (range 19–29) and an average size of the lesion of 3.5 cm2 (range 2–6). All patients underwent a single-stage procedure consisting in filling each defect with autologous culture-expanded mesenchymal stem cells embedded in a trimmed-to-fit commercially available biodegradable matrix. Pre-operative and post-operative evaluation included knee-related clinical and functional evaluation based on objective and subjective scores at 6, 12, 24 and 36 months and MRI evaluation of the repair tissue using the MOCART score at 12 and 24 months.
Results
Clinical outcomes recorded significant improvements (p < 0.05) at the final follow-up compared with baseline as following: all subcategories of KOOS Score, the IKDC subjective from 40.9 (range 20.7–65.6) to 76.9 (range 42–90.3), Tegner Activity Score from 3 (range 2–4) to 4 (range 3–4), VAS for pain from 6 (range 4–8) to 1 (range 0–3). All patients improve significantly their IKDC objective scores. The MRI findings showed complete filling of the defect and integration to the border zone for 65% of the patients. Two patients underwent post-operative biopsies and the histological analysis demonstrated the presence of hyaline-like tissue.
Conclusions
Adipose-derived culture-expanded mesenchymal stem cells were shown to be an efficient and safe single-stage cell-based procedure for symptomatic, full-thickness knee chondral lesions. The findings of the present study demonstrate that all patients presented significant mid-term clinical, functional and radiological improvement.
Level of evidence
IV.
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References
Barry FP, Murphy JM (2004) Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol 36:568–584
Bekkers JE, de Windt TS, Raijmakers NJ, Dhert WJ, Saris DB (2009) Validation of the Knee Injury and Osteoarthritis Outcome Score (KOOS) for the treatment of focal cartilage lesions. Osteoarthr Cartil 17:1434–1439
Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331:889–895
Bui K, Duong T, Nguyen N, Nguyen T, Le V, Mai V, Phan N, Le D, Phan N, Pham P (2014) Symptomatic knee osteoarthritis treatment using autologous adipose derived stem cells and platelet- rich plasma: a clinical study. Biomed Res Ther 1:2–8
Collins NJ, Misra D, Felson DT, Crossley KM, Roos EM (2011) 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) 63(Suppl 11):S208–S228
Delcogliano M, de Caro F, Scaravella E, Ziveri G, De Biase CF, Marotta D et al (2014) Use of innovative biomimetic scaffold in the treatment for large osteochondral lesions of the knee. Knee Surg Sports Traumatol Arthrosc 22:1260–1269
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317
Freitag J, Bates D, Wickham J, Shah K, Huguenin L, Tenen A et al (2019) Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Regen Med 14:213–230
Gobbi A, Karnatzikos G, Sankineani SR (2014) One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee. Am J Sports Med 42:648–657
Gobbi A, Karnatzikos G, Scotti C, Mahajan V, Mazzucco L, Grigolo B (2011) One-step cartilage repair with bone marrow aspirate concentrated cells and collagen matrix in full-Thickness Knee cartilage lesions: results at 2-year follow-up. Cartilage 2:286–299
Hurley ET, Yasui Y, Gianakos AL, Seow D, Shimozono Y, Kerkhoffs G et al (2018) Limited evidence for adipose-derived stem cell therapy on the treatment of osteoarthritis. Knee Surg Sports Traumatol Arthrosc 26:3499–3507
Jo CH, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC et al (2014) Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells 32:1254–1266
Kim YS, Choi YJ, Suh DS, Heo DB, Kim YI, Ryu JS et al (2015) Mesenchymal stem cell implantation in osteoarthritic knees: is fibrin glue effective as a scaffold? Am J Sports Med 43:176–185
Koh YG, Choi YJ, Kwon OR, Kim YS (2014) Second-look arthroscopic evaluation of cartilage lesions after mesenchymal stem cell implantation in osteoarthritic knees. Am J Sports Med 42:1628–1637
Koh YG, Choi YJ, Kwon SK, Kim YS, Yeo JE (2015) Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc 23:1308–1316
Koh YG, Kwon OR, Kim YS, Choi YJ (2014) Comparative outcomes of open-wedge high tibial osteotomy with platelet-rich plasma alone or in combination with mesenchymal stem cell treatment: a prospective study. Arthroscopy 30:1453–1460
Kon E, Delcogliano M, Filardo G, Busacca M, Di Martino A, Marcacci M (2011) Novel nano-composite multilayered biomaterial for osteochondral regeneration: a pilot clinical trial. Am J Sports Med 39:1180–1190
Kraeutler MJ, Belk JW, Purcell JM, McCarty EC (2018) Microfracture versus autologous chondrocyte implantation for articular cartilage lesions in the knee: a systematic review of 5-year outcomes. Am J Sports Med 46:995–999
Maffulli N, Binfield PM, King JB (2003) Articular cartilage lesions in the symptomatic anterior cruciate ligament-deficient knee. Arthroscopy 19:685–690
Marlovits S, Singer P, Zeller P, Mandl I, Haller J, Trattnig S (2006) Magnetic resonance observation of cartilage repair tissue (MOCART) for the evaluation of autologous chondrocyte transplantation: determination of interobserver variability and correlation to clinical outcome after 2 years. Eur J Radiol 57:16–23
Oussedik S, Tsitskaris K, Parker D (2015) Treatment of articular cartilage lesions of the knee by microfracture or autologous chondrocyte implantation: a systematic review. Arthroscopy 31:732–744
Pak J, Chang JJ, Lee JH, Lee SH (2013) Safety reporting on implantation of autologous adipose tissue-derived stem cells with platelet-rich plasma into human articular joints. BMC Musculoskelet Disord 14:337
Pak J, Lee JH, Park KS, Jeong BC, Lee SH (2016) Regeneration of cartilage in human knee osteoarthritis with autologous adipose tissue-derived stem cells and autologous extracellular matrix. Biores Open Access 5:192–200
Pelttari K, Steck E, Richter W (2008) The use of mesenchymal stem cells for chondrogenesis. Injury 39(Suppl 1):S58–S65
Peterson L, Minas T, Brittberg M, Nilsson A, Sjogren-Jansson E, Lindahl A (2000) Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res 374:212–234
Peterson L, Vasiliadis HS, Brittberg M, Lindahl A (2010) Autologous chondrocyte implantation: a long-term follow-up. Am J Sports Med 38:1117–1124
Schaffler A, Buchler C (2007) Concise review: adipose tissue-derived stromal cells—basic and clinical implications for novel cell-based therapies. Stem Cells 25:818–827
Verdonk P, Dhollander A, Almqvist KF, Verdonk R, Victor J (2015) Treatment of osteochondral lesions in the knee using a cell-free scaffold. Bone Jt J 97:318–323
Wakitani S, Nawata M, Tensho K, Okabe T, Machida H, Ohgushi H (2007) Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation: three case reports involving nine defects in five knees. J Tissue Eng Regen Med 1:74–79
Acknowledgements
The authors are grateful to the radiologist Afarine Madani MD, PhD for her contribution in MR images evaluation.
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TK: data collection, writing and critical review of the paper; IM: performed surgeries, data collection, writing and critical review of the paper; EM: performed culture isolation; IM: data collection, writing the paper; CSG: performed culture isolation; RV: critical review of the paper; TK and MI have contributed equally to this article and share first authorship.
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Ethical approval for this study was approved by the Bioethics Committee of the Aristotle University of Thessaloniki (1.4.2013/34).
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Kyriakidis, T., Iosifidis, M., Michalopoulos, E. et al. Good mid-term outcomes after adipose-derived culture-expanded mesenchymal stem cells implantation in knee focal cartilage defects. Knee Surg Sports Traumatol Arthrosc 28, 502–508 (2020). https://doi.org/10.1007/s00167-019-05688-9
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DOI: https://doi.org/10.1007/s00167-019-05688-9