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Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: a 2-year randomized study

  • Arthroscopy and Sports Medicine
  • Published:
Archives of Orthopaedic and Trauma Surgery Aims and scope Submit manuscript

Abstract

Background

Cell-based strategies that combine in vitro- expanded autologous chondrocytes with matrix scaffolds are currently preferred for full-thickness cartilage lesions of the knee ≥2 cm2. Although this approach is reasonable, continuing advances in the field of cartilage repair will further expand the options available to improve outcomes.

Hypothesis/purpose

In the present clinical study, we compared the outcomes of matrix-induced autologous mesenchymal stem cell implantation (m-AMI) with matrix-induced autologous chondrocyte implantation (m-ACI) for the treatment of isolated chondral defects of the knee.

Study design

Prospective, single-site, randomized, single-blind pilot study.

Methods

Fourteen patients with isolated full-thickness chondral lesions of the knee >2 cm2 were randomized into two treatment groups: m-AMI and m-ACI. Outcomes were assessed pre-operatively and 3, 6, 12 and 24 months post-operatively.

Results

Clinical evaluations revealed that improvement from pre-operation to 24 months post-operation occurred in both groups (p < 0.05). At all follow-up intervals, m-AMI demonstrated significantly better functional outcomes (motion deficit and straight leg raise strength) than did m-ACI (p < 0.05). At all follow-up intervals, m-AMI demonstrated significantly better subjective sub-scale scores for pain, symptoms, activities of daily living and sport and recreation of the knee injury and osteoarthritis outcome score (KOOS) than did m-ACI (p < 0.05). Additionally, m-AMI demonstrated significantly better (p < 0.05) scores than m-ACI for the quality of life sub-scale of the KOOS and visual analog scale (VAS) severity at the 6-month follow-up. The Tegner activity score and VAS frequency were not significantly different between the two groups. Graft failure was not observed on magnetic resonance imaging at the 24-month follow-up. m-AMI and m-ACI demonstrated very good-to-excellent and good-to-very good infill, respectively, with no adverse effects from the implant, regardless of the treatment.

Conclusion

For the treatment of isolated full-thickness chondral lesion of the knee, m-AMI can be used effectively and may potentially accelerate recovery. A larger patient cohort and follow-up supported by histological analyses are necessary to determine long-term outcomes.

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References

  1. Buckwalter JA, Mankin HJ (1998) Articular cartilage repair and transplantation. Arthritis Rheum 41(8):1331–1342

    Article  CAS  PubMed  Google Scholar 

  2. Mankin HJ (1974) The reaction of articular cartilage to injury and osteoarthritis (first of two parts). N Engl J Med 291(24):1285–1292

    Article  CAS  PubMed  Google Scholar 

  3. Mankin HJ (1974) The reaction of articular cartilage to injury and osteoarthritis (second of two parts). N Engl J Med 291(25):1335–1340

    Article  CAS  PubMed  Google Scholar 

  4. King PJ, Bryant T, Minas T (2002) Autologous chondrocyte implantation for chondral defects of the knee: indications and technique. J Knee Surg 15(3):177–184

    PubMed  Google Scholar 

  5. Micheli LJ, Browne JE, Erggelet C, Fu F, Mandelbaum B, Moseley JB, Zurakowski D (2001) Autologous chondrocyte implantation of the knee: multicenter experience and minimum 3-year follow-up. Clin J Sport Med 11(4):223–228

    Article  CAS  PubMed  Google Scholar 

  6. Barry FP, Murphy JM (2004) Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol 36(4):568–584

    Article  CAS  PubMed  Google Scholar 

  7. Spector TD, Cooper C (1993) Radiographic assessment of osteoarthritis in population studies: whither Kellgren and Lawrence? Osteoarthritis Cartilage 1(4):203–206

    Article  CAS  PubMed  Google Scholar 

  8. Jones E, Yang X (2011) Mesenchymal stem cells and bone regeneration: current status. Injury 42(6):562–568

    Article  PubMed  Google Scholar 

  9. Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98(5):1076–1084

    Article  CAS  PubMed  Google Scholar 

  10. Chen FH, Tuan RS (2008) Mesenchymal stem cells in arthritic diseases. Arthritis Res Ther 10(5):223–234

    Article  PubMed Central  PubMed  Google Scholar 

  11. Filardo G, Madry H, Jelic M, Roffi A, Cucchiarini M, Kon E (2013) Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics. Knee Surg Sports Traumatol Arthrosc 21(8):1717–1729

    Article  PubMed  Google Scholar 

  12. Petersson IF, Boegård T, Saxne T, Silman AJ, Svensson B (1997) Radiographic osteoarthritis of the knee classified by the Ahlbäck and Kellgren & Lawrence systems for the tibiofemoral joint in people aged 35-54 years with chronic knee pain. Ann Rheum Dis 56(8):493–496

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. De Bari C, Dell’Accio F, Tylzanowski P, Luyten FP (2001) Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum 44(8):1928–1942

    Article  PubMed  Google Scholar 

  14. Horwitz EM, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini FC, Deans RJ, Krause DS, Keating A (2005) International society for cellular therapy. Clarification of the nomenclature for MSC: the international society for cellular therapy position statement. Cytotherapy 7(5):393–395

    Article  CAS  PubMed  Google Scholar 

  15. Grogan SP, Barbero A, Diaz-Romero J, Cleton-Jansen AM, Soeder S, Whiteside R, Hogendoorn PC, Farhadi J, Aigner T, Martin I, Mainil-Varlet P (2007) Identification of markers to characterize and sort human articular chondrocytes with enhanced in vitro chondrogenic capacity. Arthritis Rheum 56(2):586–595

    Article  PubMed  Google Scholar 

  16. David W, Zheng MH (2007) Matrix-induced autologous chondrocyte implantation. In: Williams RJ (ed) Cartilage repair strategies, 1st edn. Humana Press Inc, Totowa, p 198

  17. Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD (1998) Knee Injury and Osteoarthritis Outcome Score (KOOS): development of a self-administered outcome measure. J Orthop Sports Phys Ther 28(2):88–96

    Article  CAS  PubMed  Google Scholar 

  18. Tegner Y, Lysholm J (1985) Rating systems in the evaluation of knee ligament injuries. Clin Orthop Relat Res 198:43–49

    PubMed  Google Scholar 

  19. Ebert JR, Robertson WB, Lloyd DG, Zheng MH, Wood DJ, Ackland T (2008) Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): comparison of clinical, biomechanical and radiographic outcomes. Osteoarthritis Cartilage 16(10):1131–1140

    Article  CAS  PubMed  Google Scholar 

  20. 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(1):16–23

    Article  PubMed  Google Scholar 

  21. Wondrasch B, Zak L, Welsch GH, Marlovits S (2009) Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle on radiographic and clinical outcome after 2 years: a prospective, randomized controlled pilot study. Am J Sports Med 37(Suppl 1):88S–96S

    Article  PubMed  Google Scholar 

  22. Ebert JR, Robertson WB, Lloyd DG, Zheng MH, Wood DJ, Ackland T (2010) A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes. Cartilage 1(3):180–187

    Article  Google Scholar 

  23. Ebert JR, Robertson WB, Woodhouse J, Fallon M, Zheng MH, Ackland T, Wood DJ (2011) Clinical and magnetic resonance imaging-based outcomes to 5 years after matrix-induced autologous chondrocyte implantation to address articular cartilage defects in the knee. Am J Sports Med 39(4):753–763

    Article  PubMed  Google Scholar 

  24. Ebert JR, Smith A, Edwards PK, Hambly K, Wood DJ, Ackland TR (2013) Factors predictive of outcome 5 years after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint. Am J Sports Med 41(6):1245–1254

    Article  PubMed  Google Scholar 

  25. Marlovits S, Aldrian S, Wondrasch B, Zak L, Albrecht C, Welsch G, Trattnig S (2012) Clinical and radiological outcomes 5 years after matrix-induced autologous chondrocyte implantation in patients with symptomatic, traumatic chondral defects. Am J Sports Med 40(10):2273–2280

    Article  PubMed  Google Scholar 

  26. Rosenberger RE, Gomoll AH, Bryant T, Minas T (2008) Repair of large chondral defects of the knee with autologous chondrocyte implantation in patients 45 years or older. Am J Sports Med 36(12):2336–2344

    Article  PubMed  Google Scholar 

  27. Chung CB, Frank LR, Resnick D (2001) Cartilage imaging techniques: current clinical applications and state of the art imaging. Clin Orthop Relat Res 391(Suppl):S370–S378

    Article  PubMed  Google Scholar 

  28. Edwards PK, Ackland TR, Ebert JR (2013) Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: early clinical and radiological outcomes. Am J Sports Med 41(10):2314–2324

    Article  PubMed  Google Scholar 

  29. Jones DG, Peterson L (2007) Autologous chondrocyte implantation. In: Williams RJ (ed) Cartilage repair strategies, 1st edn. Humana Press Inc, Totowa, pp 160–161

    Google Scholar 

  30. Kuroda R, Ishida K, Matsumoto T, Akisue T, Fujioka H, Mizuno K, Ohgushi H, Wakitani S, Kurosaka M (2007) Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells. Osteoarthritis Cartilage 15(2):226–231

    Article  CAS  PubMed  Google Scholar 

  31. Wakitani S, Mitsuoka T, Nakamura N, Toritsuka Y, Nakamura Y, Horibe S (2004) Autologous bone marrow stromal cell transplantation for repair of full-thickness articular cartilage defects in human patellae: two case reports. Cell Transplant 13(5):595–600

    Article  PubMed  Google Scholar 

  32. 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(1):74–79

    Article  PubMed  Google Scholar 

  33. Williams RJ, Brophy RH (2007) Decision making in cartilage repair procedures. In: Williams RJ (ed) Cartilage repair strategies, 1st edn. Humana Press Inc, Totowa p 45

  34. Wakitani S, Okabe T, Horibe S, mitsuoka, T., Saito M, Koyama T, Nawata M, Tensho K, Kato H, Uematsu K, Kuroda R, Kurosaka M, Yoshiya S, Hattori K, Ohgushi H (2010) Safety of autologous bone marrow-derived mesenchymal stem cell transplantation for cartilage repair in 41 patients with 45 joints followed for up to 11 years and 5 months. J Tissue Eng Regen Med 5(2):146–150

  35. Nejadnik H, Hui JH, Choong EPF, Tai B, Lee EH (2010) Autologous Bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med 38(6):1110–1116

    Article  PubMed  Google Scholar 

  36. Haleem AM, Singergy AAE, Sabry D, Atta HM, Rashed LA, Chu CR, Shewy MTE, Azzam A, Aziz MTA (2010) The clinical use of human culture-expanded autologous bone marrow mesenchymal stem cells transplanted on plateletrich fibrin glue in the treatment of articular cartilage defects: a pilot study and preliminary results. Cartilage 1(4):253–261

    Article  PubMed Central  PubMed  Google Scholar 

  37. Vidal MA, Robinson SO, Lopez MJ, Paulsen DB, Borkhsenious O, Johnson JR, Moore RM, Gimble JM (2008) Comparison of chondrogenic potential in equine mesenchymal stromal cells derived from adipose tissue and bone marrow. Vet Surg 37(8):713–724

    Article  PubMed Central  PubMed  Google Scholar 

  38. Yoshimura H, Muneta T, Nimura A, Yokoyama A, Koga H, Sekiya I (2007) Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle. Cell Tissue Res 327(3):449–462

    Article  CAS  PubMed  Google Scholar 

  39. De Bari C, Dell’Accio F, Karystinou A, Guillot PV, Fisk NM, Jones EA, McGonagle D, Khan IM, Archer CW, Mitsiadis TA, Donaldson AN, Luyten FP, Pitzalis C (2008) A biomarker-based mathematical model to predict bone-forming potency of human synovial and periosteal mesenchymal stem cells. Arthritis Rheum 58(1):240–250

    Article  PubMed  Google Scholar 

  40. Behrens P, Bitter T, Kurz B, Russlies M (2006) Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI): 5-year follow-up. Knee 13(3):194–202

    Article  PubMed  Google Scholar 

  41. Genovese E, Ronga M, Angeretti MG, Novario R, Leonardi A, Albrizio M, Callegari L, Fugazzola C (2011) Matrix-induced autologous chondrocyte implantation of the knee: mid-term and long-term follow-up by MR arthrography. Skeletal Radiol 40(1):47–56

    Article  PubMed  Google Scholar 

  42. Gobbi A, Kon E, Berruto M, Filardo G, Delcogliano M, Boldrini L, Bathan L, Marcacci M (2009) Patellofemoral full-thickness chondral defects treated with second-generation autologous chondrocyte implantation: results at 5 years’ follow-up. Am J Sports Med 37(6):1083–1092

    Article  PubMed  Google Scholar 

  43. Ebert JR, Robertson WB, Woodhouse J, Fallon M, Zheng MH, Ackland T, Wood DJ (2011) Clinical and magnetic resonance imaging-based outcomes to 5 years after matrix-induced autologous chondrocyte implantation to address articular cartilage defects in the knee. Am J Sports Med 39(4):753–763

    Article  PubMed  Google Scholar 

  44. Kon E, Di Martino A, Filardo G, Tetta C, Busacca M, Iacono F, Delcogliano M, Albisinni U, Marcacci M (2011) Second-generation autologous chondrocyte transplantation: MRI findings and clinical correlations at a minimum 5-year follow-up. Eur J Radiol 79(3):382–388

    Article  CAS  PubMed  Google Scholar 

  45. Nehrer S, Dorotka R, Domayer S, Stelzeneder D, Kotz R (2009) Treatment of full-thickness chondral defects with hyalograft C in the knee: a prospective clinical case series with 2 to 7 years’ follow-up. Am J Sports Med 37(suppl 1):81S–87S

    Article  PubMed  Google Scholar 

  46. Saris DB, Vanlauwe J, Victor J, Almqvist KF, Verdonk R, Bellemans J, Luyten FP, TIG/ACT/01/2000&EXT Study Group (2009) Treatment of symptomatic cartilage defects of the knee: characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture. Am J Sports Med 37(Suppl 1):10S–19S

    Article  PubMed  Google Scholar 

  47. Hambly K, Bobic V, Wondrasch B, Van Assche D, Marlovits S (2006) Autologous chondrocyte implantation postoperative care and rehabilitation: science and practice. Am J Sports Med 34:1020–1038

    Article  PubMed  Google Scholar 

  48. Bachmann G, Basad E, Lommel D, Steinmeyer J (2004) MRI in the follow-up of matrix-supported autologous chondrocyte transplantation (MACI) and microfracture. Radiologe 44(8):773–782

    Article  CAS  PubMed  Google Scholar 

  49. Henderson IJ, Tuy B, Connell D, Oakes B, Hettwer WH (2003) Prospective clinical study of autologous chondrocyte implantation and correlation with MRI at three and 12 months. J Bone Joint Surg Br 85(7):1060–1066

    Article  CAS  PubMed  Google Scholar 

  50. Marlovits S, Striessnig G, Kutscha-Lissberg F, Resinger C, Aldrian SM, Vécsei V, Trattnig S (2005) Early postoperative adherence of matrix-induced autologous chondrocyte implantation for the treatment of full-thickness cartilage defects of the femoral condyle. Knee Surg Sports Traumatol Arthrosc 13(6):451–457

    Article  PubMed  Google Scholar 

  51. Russlies M, Behrens P, Ehlers EM, Bröhl C, Vindigni C, Spector M, Kurz B (2005) Periosteum stimulates subchondral bone densification in autologous chondrocyte transplantation in a sheep model. Cell Tissue Res 319(1):133–142

    Article  PubMed  Google Scholar 

  52. Matzat SJ, van Tiel J, Gold GE, Oei EH (2013) Quantitative MRI techniques of cartilage composition. Quant Imaging Med Surg 3(3):162–174

    PubMed Central  PubMed  Google Scholar 

  53. Stelzeneder D, Shetty AA, Kim SJ, Trattnig S, Domayer SE, Shetty V, Bilagi P (2013) Repair tissue quality after arthroscopic autologous collagen-induced chondrogenesis (ACIC) assessed via T2* mapping. Skeletal Radiol 42(12):1657–1664

    Article  PubMed  Google Scholar 

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Conflict of interest

All named authors hereby declare that they have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Orthopaedics and Traumatology, Cactus Healthcare, Istanbul, Turkey

    Isık Akgun

  2. Department of Orthopedics and Traumatology, Cerrahpasa Medical Faculty, Istanbul University, 34303, Kocamustafapasa, Istanbul, Turkey

    Mehmet C. Unlu, Ozan A. Erdal & Tahir Ogut

  3. Department of Medical Microbiology, Karadeniz Technical University, Trabzon, Turkey

    Murat Erturk

  4. Labcell, Istanbul, Turkey

    Ercument Ovali

  5. Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey

    Fatih Kantarci

  6. Department of Orthopedics and Traumatology, Kanuni Sultan Suleyman State Hospital, Istanbul, Turkey

    Gurkan Caliskan

  7. Genetics and Molecular Biologist, Cellular Biologist, Trinity School of Medicine, Atlanta, USA

    Yamac Akgun

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  1. Isık Akgun
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  2. Mehmet C. Unlu
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Correspondence to Mehmet C. Unlu.

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Akgun, I., Unlu, M.C., Erdal, O.A. et al. Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: a 2-year randomized study. Arch Orthop Trauma Surg 135, 251–263 (2015). https://doi.org/10.1007/s00402-014-2136-z

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  • DOI: https://doi.org/10.1007/s00402-014-2136-z

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