Top

Current Reviews in Musculoskeletal Medicine

Published in:

01-09-2012 | Sports non-ACL (TS Wanich, Section Editor)

New trends for knee cartilage regeneration: from cell-free scaffolds to mesenchymal stem cells

Authors: Elizaveta Kon, Giuseppe Filardo, Alice Roffi, Luca Andriolo, Maurilio Marcacci

Published in: Current Reviews in Musculoskeletal Medicine | Issue 3/2012

Abstract

In the last decade, huge steps forward have been made in the field of cartilage regeneration. The most recent trend for treating chondral/osteochondral lesions is based on the application of smart biomaterials that could lead to “in situ” regeneration of not only cartilage, but also subchondral bone, preferably through a single step procedure to reduce the costs and the morbidity for the patient. This innovative approach is currently under investigation as several “scaffolds” have been proposed in clinical practice, with or without the aid of cells, with the opportunity, in the second case, of bypassing the strict limits imposed by cell manipulation regulations. Furthermore, the fascinating potential of mesenchymal stem cells has recently opened new paths of research to discover how and whether these powerful entities can really contribute to tissue regeneration. The first clinical trials have been published but further high quality research is needed to understand their mechanisms of action, their limits, and their clinical efficacy.

Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994;331:889–95.PubMedCrossRef

• Peterson L, Vasiliadis HS, Brittberg M, Lindahl A. Autologous chondrocyte implantation: a long-term follow-up. Am J Sports Med. 2010;38:1117–24. First generation ACI offers good long-term results with stable results over time.PubMedCrossRef

Vasiliadis HS, Danielson B, Ljungberg M, McKeon B, Lindahl A, Peterson L. Autologous chondrocyte implantation in cartilage lesions of the knee: long-term evaluation with magnetic resonance imaging and delayed gadolinium-enhanced magnetic resonance imaging technique. Am J Sports Med. 2010;38:943–9.PubMedCrossRef

Peterson L, Brittberg M, Kiviranta I, Akerlund EL, Lindahl A. Autologous chondrocyte transplantation. Biomechanics and long-term durability. Am J Sports Med. 2002;30:2–12.PubMed

Browne JE, Anderson AF, Arciero R, Mandelbaum B, Moseley JB Jr, Micheli LJ, et al. Clinical outcome of autologous chondrocyte implantation at 5 years in US subjects. Clin Orthop Relat Res. 2005;436:237–45.PubMedCrossRef

Micheli LJ, Browne JE, Erggelet C, Fu F, Mandelbaum B, Moseley JB, et al. Autologous chondrocyte implantation of the knee: multicenter experience and minimum 3-year follow-up. Clin J Sport Med. 2001;11:223–8.PubMedCrossRef

Kon E, Delcogliano M, Filardo G, Montaperto C, Marcacci M. Second generation issues in cartilage repair. Sports Med Arthrosc. 2008;16:221–9.PubMedCrossRef

Grigolo B, Lisignoli G, Piacentini A, Fiorini M, Gobbi P, Mazzotti G, et al. Evidence for redifferentiation of human chondrocytes grown on a hyaluronan-based biomaterial (HYAff 11): molecular, immunohistochemical and ultrastructural analysis. Biomaterials. 2002;23:1187–95.PubMedCrossRef

• Kon E, Verdonk P, Condello V, Delcogliano M, Dhollander A, Filardo G, et al. Matrix-assisted autologous chondrocyte transplantation for the repair of cartilage defects of the knee: systematic clinical data review and study quality analysis. Am J Sports Med. 2009;37 Suppl 1:156S–66S. Many procedures have been developed using different scaffolds for three dimensional cell transplant addressing biological and surgical concerns of the first generation ACI and providing a good medium-term outcome.PubMedCrossRef

10.

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

11.

Ferruzzi A, Buda R, Faldini C, Vannini F, Di Caprio F, Luciani D, et al. Autologous chondrocyte implantation in the knee joint: open compared with arthroscopic technique. Comparison at a minimum follow-up of five years. J Bone Joint Surg Am. 2008;90 Suppl 4:90–101.PubMedCrossRef

12.

Kon E, Di Martino A, Filardo G, Tetta C, Busacca M, Iacono F, et al. Second-generation autologous chondrocyte transplantation: MRI findings and clinical correlations at a minimum 5-year follow-up. Eur J Radiol. 2011;79:382–8.PubMedCrossRef

13.

Kon E, Filardo G, Berruto M, Benazzo F, Zanon G, Della Villa S, et al. Articular cartilage treatment in high-level male soccer players: a prospective comparative study of arthroscopic second-generation autologous chondrocyte implantation vs microfracture. Am J Sports Med. 2011;39:2549–57.PubMedCrossRef

14.

Kon E, Filardo G, Condello V, Collarile M, Di Martino A, Zorzi C, et al. Second-Generation Autologous Chondrocyte Implantation: results in patients older than 40 years. Am J Sports Med. 2011;39:1668–75.PubMedCrossRef

15.

Kon E, Gobbi A, Filardo G, Delcogliano M, Zaffagnini S, et al. Arthroscopic second-generation autologous chondrocyte implantation compared with microfracture for chondral lesions of the knee: prospective nonrandomized study at 5 years. Am J Sports Med. 2009;37:33–41.PubMedCrossRef

16.

Gobbi A, Kon E, Berruto M, Filardo G, Delcogliano M, Boldrini L, et al. Patellofemoral full-thickness chondral defects treated with second-generation autologous chondrocyte implantation: results at 5 years' follow-up. Am J Sports Med. 2009;37:1083–92.PubMedCrossRef

17.

Filardo G, Kon E, Berruto M, Di Martino A, Patella S, Marcheggiani Muccioli GM, et al. Arthroscopic second generation autologous chondrocytes implantation associated with bone grafting for the treatment of knee osteochondritis dissecans: results at 6 years. Knee. 2011;Nov 22.

18.

Filardo G, Kon E, Di Martino A, Patella S, Altadonna G, Balboni F, et al. Second-generation arthroscopic autologous chondrocyte implantation for the treatment of degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc. 2011;Nov 1.

19.

Filardo G, Kon E, Di Martino A, Iacono F, Marcacci M. Arthroscopic second-generation autologous chondrocyte implantation: a prospective 7-year follow-up study. Am J Sports Med. 2011;39:2153–60.PubMedCrossRef

20.

Nehrer S, Dorotka R, Domayer S, Stelzeneder D, Kotz R. 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. 2009;37 Suppl 1:81S–7S.

21.

Ebert JR, Robertson WB, Woodhouse J, Fallon M, Zheng MH, Ackland T, et al. 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. 2011;39:753–63.PubMedCrossRef

22.

Macmull S, Jaiswal PK, Bentley G, Skinner JA, Carrington RW, Briggs TW. The role of autologous chondrocyte implantation in the treatment of symptomatic chondromalacia patellae. Int Orthop. 2012;36:1371–7.

23.

Marcacci M, Zaffagnini S, Kon E, Visani A, Iacono F, Loreti I. Arthroscopic autologous chondrocyte transplantation: technical note. Knee Surg Sports Traumatol Arthrosc. 2002;10:154–9.PubMedCrossRef

24.

Erggelet C, Sittinger M, Lahm A. The arthroscopic implantation of autologous chondrocytes for the treatment of full-thickness cartilage defects of the knee joint. Arthroscopy. 2003;19:108–10.PubMed

25.

Gobbi A, Bathan L. Biological approaches for cartilage repair. J Knee Surg. 2009;22:36–44.PubMedCrossRef

26.

Cole BJ, Farr J, Winalski CS, Hosea T, Richmond J, Mandelbaum B, et al. Outcomes after a single-stage procedure for cell-based cartilage repair: a prospective clinical safety trial with 2-year follow-up. Am J Sports Med. 2011;39:1170–9.

27.

Buda R, Vannini F, Cavallo M, Grigolo B, Cenacchi A, Giannini S. Osteochondral lesions of the knee: a new one-step repair technique with bone-marrow-derived cells. J Bone Joint Surg Am. 2010;92 Suppl 2:2–11.

28.

Gobbi A, Karnatzikos G, Scotti C, Mahajan V, Mazzucco L, Grigolo B. 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. 2011;2:286–299.CrossRef

29.

Almqvist KF, Dhollander AA, Verdonk PC, Forsyth R, Verdonk R, Verbruggen G. Treatment of cartilage defects in the knee using alginate beads containing human mature allogenic chondrocytes. Am J Sports Med. 2009;37:1920–9.PubMedCrossRef

30.

Gille J, Schuseil E, Wimmer J, Gellissen J, Schulz AP, Behrens P. Mid-term results of Autologous Matrix-Induced Chondrogenesis for treatment of focal cartilage defects in the knee. Knee Surg Sports Traumatol Arthrosc. 2010;18:1456–64.

31.

Patrascu JM, Freymann U, Kaps C, Poenaru DV. Repair of a post-traumatic cartilage defect with a cell-free polymer-based cartilage implant: a follow-up at two years by MRI and histological review. J Bone Joint Surg Br. 2010;92:1160–3.PubMedCrossRef

32.

Pascarella A, Ciatti R, Pascarella F, Latte C, Di Salvatore MG, Liguori L, et al. Treatment of articular cartilage lesions of the knee joint using a modified AMIC technique. Knee Surg Sports Traumatol Arthrosc. 2010;18:509–13.PubMedCrossRef

33.

Dhollander AA, De Neve F, Almqvist KF, Verdonk R, Lambrecht S, Elewaut D, et al. Autologous matrix-induced chondrogenesis combined with platelet-rich plasma gel: technical description and a five pilot patients report. Knee Surg Sports Traumatol Arthrosc. 2011;19:536–42.

34.

Schiavone Panni A, Cerciello S, Vasso M. The manangement of knee cartilage defects with modified amic technique: preliminary results. Int J Immunopathol Pharmacol. 2011;24(1 Suppl 2):149–52.PubMed

35.

Kusano T, Jakob RP, Gautier E, Magnussen RA, Hoogewoud H, Jacobi M. Treatment of isolated chondral and osteochondral defects in the knee by autologous matrix-induced chondrogenesis (AMIC). Knee Surg Sports Traumatol Arthrosc. 2011;Dec 25.

36.

Pape D, Filardo G, Kon E, van Dijk CN, Madry H. Disease-specific clinical problems associated with the subchondral bone. Knee Surg Sports Traumatol Arthrosc. 2010;18:448–62.

37.

Kon E, Mutini A, Arcangeli E, Delcogliano M, Filardo G, Nicoli Aldini N, et al. Novel nanostructured scaffold for osteochondral regeneration: pilot study in horses. J Tissue Eng Regen Med. 2010;4:300–8.

38.

Kon E, Filardo G, Delcogliano M, Fini M, Salamanna F, Giavaresi G. Platelet autologous growth factors decrease the osteochondral regeneration capability of a collagen-hydroxyapatite scaffold in a sheep model. BMC Musculoskelet Disord. 2010;11:220.

39.

Barber FA, Dockery WD. A computed tomography scan assessment of synthetic multiphase polymer scaffolds used for osteochondral defect repair. Arthroscopy. 2011;27:60–4.PubMedCrossRef

40.

Bedi A, Foo LF, Williams RJ, Potter HG, the Cartilage Study Group. The maturation of synthetic scaffolds for osteochondral donor sites of the knee: an MRI and T2-Mapping Analysis. Cartilage. 2010;1:20–8.

41.

Carmont MR, Carey-Smith R, Saithna A, Dhillon M, Thompson P, Spalding T. Delayed incorporation of a TruFit plug: perseverance is recommended. Arthroscopy. 2009;25:810–4.

42.

Kon E, Delcogliano M, Filardo G, Fini M, Giavaresi G, Francioli S, et al. Orderly osteochondral regeneration in a sheep model using a novel nano-composite multilayered biomaterial. J Orthop Res. 2010;28:116–24.

43.

Kon E, Delcogliano M, Filardo G, Pressato D, Busacca M, Grigolo B, et al. A novel nano-composite multi-layered biomaterial for treatment of osteochondral lesions: technique note and an early stability pilot clinical trial. Injury. 2010;41:693–701.

44.

Kon E, Delcogliano M, Filardo G, Altadonna G, Marcacci M. Novel nano-composite multi-layered biomaterial for the treatment of multifocal degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc. 2009;17:1312–25.PubMedCrossRef

45.

Kon E, Delcogliano M, Filardo G, Busacca M, Di Martino A, Marcacci M. Novel nano-composite multilayered biomaterial for osteochondral regeneration: a pilot clinical trial. Am J Sports Med. 2011;39:1180–90.

46.

Friedenstein AJ, Gorskaja JF, Kulagina NN. Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol. 1976;4:267–74.PubMed

47.

Smith GD, Knutsen G, Richardson JB. A clinical review of cartilage repair techniques. J Bone Joint Surg Br. 2005;87:445–9.PubMedCrossRef

48.

Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98:1076–84.PubMedCrossRef

49.

Lodi D, Iannitti T, Palmieri B. Stem cells in clinical practice: applications and warnings. J Exp Clin Cancer Res. 2011;30:9.PubMedCrossRef

50.

Wakitani S, Goto T, Pineda SJ, Young RG, Mansour JM, Caplan AI, Goldberg VM. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am. 1994;76:579–92.

51.

Caplan AI, Elyaderani M, Mochizuki Y, Wakitani S, Goldberg VM. Principles of cartilage repair and regeneration. Clin Orthop Relat Res. 1997;342:254–69.

52.

Chen FH, Tuan RS. Mesenchymal stem cells in arthritic diseases. Arthritis Res Ther. 2008;10:223–34.PubMedCrossRef

53.

Sundin M, Ringdén O, Sundberg B, Nava S, Götherström C, Le Blanc K. No alloantibodies against mesenchymal stromal cells, but presence of anti-fetal calf serum antibodies, after transplantation in allogeneic hematopoietic stem cell recipients. Haematologica. 2007;92:1208–15.

54.

Sakaguchi Y, Sekiya I, Yagishita K, Muneta T. Comparison of human stem cells derived from various mesenchymal tissues. Superiority of synovium as a cell source. Arthritis Rheum. 2005;52:2521–9.PubMedCrossRef

55.

Mosna F, Sensebé L, Krampera M. Human bone marrow and adipose tissue mesenchymal stem cells: a user's guide. Stem Cells Dev. 2010;19:1449–70.PubMedCrossRef

56.

Krampera M, Pizzolo G, Aprili G, Franchini M. Mesenchymal stem cells for bone, cartilage, tendon and skeletal muscle repair. Bone. 2006;39:678–83.PubMedCrossRef

57.

Noth U, Steinert AF, Tuan RS. Technology insight: adult mesenchymal stem cells for osteoarthritis therapy. Nat Clin Pract Rheumatol. 2008;4:371–80.PubMed

58.

Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, Yoneda M. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage. 2002;10:199–206.

59.

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

60.

Kuroda R, Ishida K, Matsumoto T, Akisue T, Fujioka H, Mizuno K, et al. Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells. Osteoarthritis Cartilage. 2007;15:226–31.

61.

Kasemkijwattana C, Hongeng S, Kesprayura S, Rungsinaporn V, Chaipinyo K, Chansiri K. Autologous bone marrow mesenchymal stem cells implantation for cartilage defects: two cases report. J Med Assoc Thai. 2011;94:395–400.PubMed

62.

Adachi N, Ochi M, Deie M, Ito Y. Transplant of mesenchymal stem cells and hydroxyapatite ceramics to treat severe osteochondral damage after septic arthritis of the knee. J Rheumatol. 2005;32:1615–8.PubMed

63.

Haleem AM, Singergy AA, Sabry D, Atta HM, Rashed LA, Chu CR, et al. The clinical use of human culture-expanded autologous bone marrow mesenchymal stem cells transplanted on Platelet-Rich Fibrin Glue in the treatment of Articular Cartilage Defects: a pilot study and preliminary results. Cartilage. 2010;1:253–61.

64.

• Nejadnik H, Hui JH, Feng Choong EP, Tai BC, Lee EH. Autologous bone marrow-derived mesenchymal stem cells vs autologous chondrocyte implantation: an observational cohort study. Am J Sports Med. 2010;38:1110–6. The Comparison Between Autologous Chondrocyte Implantation And Autologous Bone Marrow-Derived Mesenchymal Stem Cells Implantation Showed The Potential Advantage Of The New Cell-Based Approach, With Similar Results But Lower Cost And Morbidity With Respect To The Classic ACI Technique.

65.

Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician. 2008;11:343–53.

66.

Davatchi F, Abdollahi BS, Mohyeddin M, Shahram F, Nikbin B. Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients. Int J Rheum Dis. 2011;14:211–5.

67.

Gigante A, Calcagno S, Cecconi S, Ramazzotti D, Manzotti S, Enea D. Use of collagen scaffold and autologous bone marrow concentrate as a one-step cartilage repair in the knee: histological results of second-look biopsies at 1 year follow-up. Int J Immunopathol Pharmacol. 2011;24(1 Suppl 2):69–72.

68.

Wagner W, Wein F, Seckinger A, Frankhauser M, Wirkner U, Krause U, et al. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol. 2005;33:1402–16.

69.

Schäffler A, Büchler C. Concise review: adipose tissue-derived stromal cells–basic and clinical implications for novel cell-based therapies. Stem Cells. 2007;25:818–27.PubMedCrossRef

70.

Im GI, Lee JH. Repair of osteochondral defects with adipose stem cells and a dual growth factor-releasing scaffold in rabbits. J Biomed Mater Res B Appl Biomater. 2010;92:552–60.PubMed

71.

Pak J. Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series. J Med Case Rep. 2011;5:296.PubMedCrossRef

72.

Selmi TA, Verdonk P, Chambat P, Dubrana F, Potel JF, Barnouin L, et al. Autologous chondrocyte implantation in a novel alginate-agarose hydrogel: outcome at two years. J Bone Joint Surg Br. 2008;90:597–604.

Title: New trends for knee cartilage regeneration: from cell-free scaffolds to mesenchymal stem cells
Authors: Elizaveta Kon
Giuseppe Filardo
Alice Roffi
Luca Andriolo
Maurilio Marcacci
Publication date: 01-09-2012
Publisher: Current Science Inc.
Published in: Current Reviews in Musculoskeletal Medicine / Issue 3/2012
Electronic ISSN: 1935-9748
DOI: https://doi.org/10.1007/s12178-012-9135-x

At a glance: The STEP trials

Springer Medicine

New trends for knee cartilage regeneration: from cell-free scaffolds to mesenchymal stem cells

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2012

Humeral shaft fractures

Management of cartilage defects in the shoulder

Fragility fractures of the pelvis

Operative treatment of chondral defects in the hip joint: a systematic review

Femoral head fractures

Acute compartment syndrome: obtaining diagnosis, providing treatment, and minimizing medicolegal risk