Autologous chondrocyte transplant

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The autologous chondrocyte transplantation (ACT) , also known as autologous chondrocyte transplantation or autologous chondrocyte implantation referred to is a method of treatment of cartilage damage . For this purpose, autologous , i.e. the body's own cartilage cells ( chondrocytes ) are removed, multiplied in a nutrient solution and, after being introduced into a carrier material, introduced into the cartilage defect. The aim of ACT is to reduce clinical symptoms of cartilage damage and to prevent the development of (secondary) osteoarthritis . The method is not yet suitable for the treatment of general damage to a joint, an existing osteoarthritis.

Procedure

In a first operation, cartilage cells are removed from a less stressed area of ​​the affected joint. These are now propagated in vitro in a nutrient solution. After about two weeks, enough cartilage cells have been grown to implant them into the damaged cartilage. In the classic surgical method with the introduction of a cell suspension, the cartilage defect must first be closed with a periosteal flap (or an artificial membrane) after preparation (removal of loose healing tissue) in order to create a defined chamber for the cell suspension. Care is taken to ensure that this is sewn to the surrounding cartilage in a watertight manner. The suspension of the grown cartilage cells can then be injected under the periosteal flap. The chondrocytes present in the solution develop hyaline-like cartilage after some time and the existing damage is completely filled by the newly formed cartilage.

The method was developed in Gothenburg (Sweden) and, after successful testing on an animal model, was first used in humans in the early 1990s. The first results on this tissue engineering application were published in 1994. The procedure is now also recommended in Germany by specialist societies (e.g. the German Society for Orthopedics and Orthopedic Surgery; DGOOC) and since January 1, 2007 the costs have also been covered by the statutory health insurance companies under certain conditions.

From a medical point of view, if there is extensive cartilage damage in the knee joint, the indication for ACT is from a size of 4 cm² (for untreated cartilage damage) and from around 2.5 cm² (for cartilage damage that was previously unsuccessfully treated with an alternative method). It has now been shown that patients whose cartilage damage was primarily treated with microfracture or Pridie drilling have poorer results with ACT.

Further developments

The technology has been continuously developed since the process was introduced. A periosteum flap was primarily used to cover the cartilage cell suspension, which was usually removed from the anterior edge of the tibia with a second, albeit small, operation. Later, a porcine (= pig-derived) collagen membrane was used, which not only made the removal of the periosteum flap superfluous, but also made the occurrence of overgrowth of the transplant, which was often observed when using periosteal flaps, less common. Finally, the matrix-associated transplantation process (MACI) was introduced, in which the cartilage cells are applied to a collagen carrier substance in the laboratory or immediately before transplantation in the operating room . Even if no scientific data are available regarding an improved effectiveness of these products, this further development has led to a simpler application and use with shorter operation times.

Other developments relate to the isolation of cartilage cells. Some companies already offer cartilage cells that are grown without the patient's own serum. This leads to a standardization of the cell culture conditions and makes a blood collection from the patient for the cultivation of the cartilage cells superfluous. Other manufacturers are working on selecting cartilage cells with a particularly high cartilage synthesis capacity. Better therapeutic success through this ACT procedure has not yet been proven. Other concepts follow the principle of applying the cartilage cells in matrix clusters as spherical implants. The advantage here is that cells can be applied to defects without any fixing substances (fleeces, gels or fibrin glue). Arthroscopic applications on the kneecap are even possible overhead.

The matrix substances used during the further development of the ACT (e.g. 3-D collagen fleece) are finally also introduced in a cell-free manner ( AMIC ). For the procedure, the base of the defect is broken open with an awl and the bleeding is stimulated, releasing abundant cell material from the body with the blood. This blood-cell mixture is then caught in the applied fleece and there stimulated differentiation into cartilage-like cells. It is a modification of the microfracture technique, which is successful for small cartilage defects. The advantage here is that the critical and costly cell culture process is saved. In this way, the procedure can also be carried out at short notice and without preparation in the event of incidental findings during an arthroscopy.

Treatment successes

The treatment success of the ACT method is between 80 and 90% depending on the location of the defect, the defect configuration and the suitability of the patient. There are now also individual studies that report satisfactory long-term results. Patient satisfaction is crucial for the success of cartilage transplants. Endpoints that were previously defined, such as repair with natural articular cartilage, now take a back seat when the therapy goals are interpreted in a targeted manner. In contrast to the use on the knee joint, where therapy with autologous cartilage cells is usually reimbursed by both private and statutory health insurance companies in Germany, applications on other joints have so far been the exception.

Individual evidence

  1. ↑ P. Niemeyer, P. Kreuz, M. Steinwachs, N. Südkamp: Surgical therapy methods for the treatment of circumscribed cartilage damage to the knee joint. In: Sports injury · Sports damage. 21, 2007, pp. 41-50, doi : 10.1055 / s-2007-963030 .
  2. ^ DA Grande, MI Pitman, L. Peterson, D. Menche, M. Klein: The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation. In: Journal of orthopedic research: official publication of the Orthopedic Research Society Volume 7, Number 2, 1989, pp. 208-218, ISSN  0736-0266 . doi : 10.1002 / jor.1100070208 . PMID 2918421 .
  3. ↑ M. Brittberg, A. Lindahl, A. Nilsson, C. Ohlsson, O. Isaksson, L. Peterson: Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. In: The New England Journal of Medicine Volume 331, Number 14, October 1994, pp. 889-895, ISSN  0028-4793 . doi : 10.1056 / NEJM199410063311401 . PMID 8078550 .
  4. ↑ P. Behrens, U. Bosch, J. Bruns, C. Erggelet, SA Esenwein, C. Gaissmaier, T. Krackhardt, J. Löhnert, S. Marlovits, NM Meenen, J. Mollenhauer, S. Nehrer, FU Niethard, U. Nöth, C. Perka, W. Richter, D. Schäfer, U. Schneider, M. Steinwachs, K. Weise: [Indications and implementation of recommendations of the working group "Tissue Regeneration and Tissue Substitutes" for autologous chondrocyte transplantation ( ACT)]. In: Journal of Orthopedics and their Border Areas Volume 142, Number 5, 2004 Sep-Oct, pp. 529-539, ISSN  0044-3220 . doi : 10.1055 / s-2004-832353 . PMID 15472761 . (Review).
  5. ↑ P. Niemeyer, PC Kreuz, M. Steinwachs, NP Südkamp: Surgical therapy methods for the treatment of circumscribed cartilage damage to the knee joint. In: Sport injury sport damage : Organ of the Society for Orthopedic-Traumatological Sports Medicine Volume 21, Number 1, March 2007, pp. 41-50, ISSN  0932-0555 . doi : 10.1055 / s-2007-963030 . PMID 17385104 . (Review).
  6. ↑ M. Steinwachs, PC Kreuz: Autologous chondrocyte implantation in chondral defects of the knee with a type I / III collagen membrane: a prospective study with a 3-year follow-up. In: Arthroscopy Volume 23, Number 4, April 2007, pp. 381-387, ISSN  1526-3231 . doi : 10.1016 / j.arthro.2006.12.003 . PMID 17418330 .
  7. ↑ P. Niemeyer, JM Pestka, PC Kreuz, C. Erggelet, H. Schmal, NP Suedkamp, ​​M. Steinwachs: Characteristic complications after autologous chondrocyte implantation for cartilage defects of the knee joint. In: The American journal of sports medicine Volume 36, Number 11, November 2008, pp. 2091-2099 , ISSN  1552-3365 . doi : 10.1177 / 0363546508322131 . PMID 18801942 .
  8. ^ CR Gooding, W. Bartlett, G. Bentley, JA Skinner, R. Carrington, A. Flanagan: A prospective, randomized study comparing two techniques of autologous chondrocyte implantation for osteochondral defects in the knee: Periosteum covered versus type I / III collagen covered. In: The Knee Volume 13, Number 3, June 2006, pp. 203-210, ISSN  0968-0160 . doi : 10.1016 / j.knee.2006.02.011 . PMID 16644224 .
  9. ↑ S. Marlovits, P. Zeller, P. Singer, C. Resinger, V. Vécsei: Cartilage repair: autologous chondrocyte transplantation generations of. In: European journal of radiology Volume 57, Number 1, January 2006, pp. 24-31, ISSN  0720-048X . doi : 10.1016 / j.ejrad.2005.08.009 . PMID 16188417 . (Review).
  10. ↑ P. Behrens, T. Bitter, B. Kurz, M. Russlies: Matrix-associated autologous chondrocyte transplantation / implantation (MACT / MACI) -5-year follow-up. In: The Knee Volume 13, Number 3, June 2006, pp. 194-202, ISSN  0968-0160 . doi : 10.1016 / j.knee.2006.02.012 . PMID 16632362 .
  11. ↑ M. Steinwachs: New technique for cell-seeded collagen-matrix-supported autologous chondrocyte transplantation. In: Arthroscopy Volume 25, Number 2, February 2009, pp. 208-211, ISSN  1526-3231 . doi : 10.1016 / j.arthro.2008.10.009 . PMID 19171282 .
  12. ↑ C. Perka, O. Schultz, M. Sittinger, H. Zippel: [Chondrocyte transplantation in PGLA / polydioxanone fleece]. In: Der Orthopäde Volume 29, Number 2, February 2000, pp. 112-119, ISSN  0085-4530 . PMID 10743632 .
  13. ↑ S. Andereya, U. Maus, K. Gavenis, R. Müller-Rath, O. Miltner, T. Mumme, U. Schneider: First clinical experiences with a new three-dimensional collagen gel (CaReS) for the treatment of focal cartilage defects in the knee joint. In: Journal of Orthopedics and their Border Areas Volume 144, Number 3, 2006 May-Jun, pp. 272-280, ISSN  0044-3220 . doi : 10.1055 / s-2006-933445 . PMID 16821178 .
  14. ↑ DB Saris, J. Vanlauwe, J. Victor, M. Haspl, M. Bohnsack, Y. Fortems, B. Vandekerckhove, KF Almqvist, T. Claes, F. trading Berg, K. Lagae, J. van der Bauwhede, H Vandenneucker, KG Yang, M. Jelic, R. Verdonk, N. Veulemans, J. Bellemans, FP Luyten: Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. In: The American journal of sports medicine Volume 36, Number 2, February 2008, pp. 235-246, ISSN  1552-3365 . doi : 10.1177 / 0363546507311095 . PMID 18202295 .
  15. ↑ MR Steinwachs, PC Kreuz: Clinical Results of Autologous Chondrocyte Transplantation (ACT) Using a Collagen Membrane Cartilage Surgery and Future Perspectives. Cartilage Surgery and Future Perspectives. Ed .: N. Hendrich, Eulert. Chapter 5, 2003, pp. 37-47.
  16. ↑ L. Peterson, T. Minas, M. Brittberg, A. Lindahl: Treatment of osteochondritis dissecans of the knee with autologous chondrocyte transplantation: results at two to ten years. In: The Journal of Bone & Joint Surgery . Volume 85-A Suppl 2, 2003, pp. 17-24, ISSN  0021-9355 . PMID 12721341 .
  17. ↑ L. Peterson, T. Minas, M. Brittberg, A. Nilsson, E. Sjögren-Jansson, A. Lindahl: Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. In: Clinical Orthopedics and Related Research Number 374, May 2000, pp. 212-234, ISSN  0009-921X . PMID 10818982 .

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