Zell- und gentherapeutische Ansätze zur Knorpelreparatur und potenziellen Arthrosetherapie

 

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Zusammenfassung

Mögliche Strategien zur Arthrosebehandlung basieren auf einer Hemmung des Matrixabbaus oder vielmehr der Steigerung des Knorpelanabolismus im erkrankten Gelenk. Die Applikation antikataboler oderantiinflammatorischerZyto- kine hat sich in Studien bereits als günstig erwiesen. Der breite klinische Einsatz dieser Ansätze wird jedoch durch die enormen Kosten aufgrund der kurzen Halbwertszeit der Proteine im Gelenk eingeschränkt. Mittels Gentransfer könnten auch über längere Zeit die erforderlichen therapeutischen Proteinkonzentrationen im erkrankten Gewebe erzielt werden. Größere Knorpelschäden und fortgeschrittene Arthrosestadien erfordern die Bildung von neuem hyalinen Knorpelgewebe. Mittels chirurgischer Verfahren gelingt es oft nicht, die Gelenkoberflächewiederherzustellen; meistens führen sie nurzur Faserknorpelbildung. In experimentellen Studien konnte durch Einsatz bestimmter Wachstums- und Differenzierungsfaktoren die Chondrogenese effizient stimuliert und hyalines knorpelähnliches Reparaturgewebe generiert werden. Zielgerichteter zellvermittelter Gentransfer könnte in idealer Weise die Bereitstellung von Knorpel(vorläufer-)zellen mit der Produktion therapeutischer Faktoren kombinieren.

Summary

Potential therapeutic strategies for cartilage injuries and osteoarthritis aim at an inhibition of matrix degradation or the stimulation of cartilage anabolism in the diseased joint. In a number ofstudies, the administration of anti-catabolic or anti-inflammatory cytokines to joints affected by cartilage destruction has proven to be beneficial. However, the clinical utility of this strategy is limited by the enormous costs dueto the short half-lives of these proteins in vivo. The transfer of the respective genes may provide a more sustained delivery of such molecules at the desired location. Lesions with substantial loss of cartilage tissue and final stages of osteoarthritis require the generation of new hyaline cartilage. Surgical approaches often fail to restore the articular surface, facing the problem of incomplete chondrogenesis. In experimental studies, certain growth and differentiation factors have proven their potential to stimulate chondrogenesis and the formation of a hyaline cartilagelike repair tissue. Targeted cell-mediated gene transfer couldideally combine thesupply of chondroprogenitorcells with the production of therapeutic factors.

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