Zusammenfassung
Hintergrund
Für präklinische Studien zu Knorpelreparaturmechanismen bestehen mehrere Großtiermodelle. Schaf, Schwein, Ziege, Hund und Pferd können aufgrund der Größenverhältnisse des Kniegelenks zu Studien der Knorpelregeneration herangezogen werden.
Material und Methoden
Hierbei können die gängigen Untersuchungsmethoden angewendet werden. Die subchondrale Lamelle wird berücksichtigt, um die Ergebnisse der Regeneration mit einer ACT oder MACT nicht durch eingewanderte Zellen aus dem Markraum zu verfälschen, obwohl die Rekrutierung von Zellen in der humanen Knorpelregeneration oft erwünscht ist. Die Defekte werden meist an den Kondylen sowie an der Trochlea, häufig bilateral, gesetzt. Dabei wird darauf geachtet, dass aufgrund der gewählten Defektgröße keine Spontanheilung auftreten kann. Die Zeiträume für eine Beurteilung der Effizienz der Knorpelregeneration liegen zwischen 6 und 12 Monaten. Für Pilotstudien werden kürzere Standzeiten bis zu 12 Wochen beschrieben. Als Auswerteverfahren dienen verschiedene Scores, die eine Histologie, Immunhistologie und die biochemische Untersuchung des Reparaturgewebes einschließen. Biomechanische Tests des Gewebes stehen am Ende der Versuche, wobei mit dem Einsatz von Schnittbildverfahren, wie dem MRT, der Verlauf einer Regeneration zusätzlich in vivo beurteilt werden kann.
Schlussfolgerung
Schritte zur Standardisierung von Großtiermodellen für die Beurteilung von regenerativen Therapieansätzen existieren kaum, sind aber aus Sicht der Zulassung neuer Ansätze und v. a. aus der Sicht des Tierschutzes anzustreben.
Abstract
Background
Several animal models are available for the analysis of regeneration of articular cartilage in large animals, such as sheep, pigs, goats, dogs and horses. The subchondral bone lamella must be considered when ACT and MACT techniques are examined in order to protect the implant against migration of cells from the bone marrow, although recruitment of cells is often desirable in the regeneration of human cartilage.
Material and methods
The defects are mainly positioned at the condyles and the trochlea often bilaterally and spontaneous healing should be excluded. The follow-up period for assessment of the effectiveness of cartilage regeneration is 6–12 months. Shorter observation times up to 12 weeks can be used for pilot studies. Scores based on histological, immunohistological and biochemical staining are mostly used for assessing the regenerated tissue. Biomechanical tests with destructive features need isolated specimens from the animal but modern slice imaging techniques can reflect the progression of the healing processes over the time span of the study in vivo.
Conclusion
Approaches to standardize the evaluation of the regeneration of articular cartilage have been sporadically described whereas they are required from the point of view of the approval of new concepts for therapy and the protection of animals.
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Danksagung
Die Autoren bedanken sich beim BMBF für die Unterstützung im Rahmen des Projekts „Funktionelle Qualitätssicherung von regenerativen Gewebeersatzmaterialien für Knorpel und Meniskus (Qu-Re-Ge)“, Förderkennzeichen 0315577G und 0315577C.
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Schneider-Wald, B., von Thaden, A. & Schwarz, M. Defektmodelle für die Gelenkknorpelregeneration im Großtier. Orthopäde 42, 242–253 (2013). https://doi.org/10.1007/s00132-012-2044-2
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DOI: https://doi.org/10.1007/s00132-012-2044-2