Gentherapie für traumatische Defekte des Gelenkknorpels

Zusammenfassung

Traumatische fokale Defekte des hyalinen Gelenkknorpels stellen ein ungelöstes Problem in der klinischen Orthopädie dar. Keine der derzeit verwendeten Therapien führt zu einer kompletten und dauerhaften Knorpelregeneration. Obwohl das Konzept einer Gentherapie für Knorpelschäden elegant erscheint, zeigt die gegenwärtige Forschung, dass die verwendeten Gentransfertechniken an das Problem eines umschriebenen Knorpeldefektes angepasst werden müssen. Insbesondere eine örtlich begrenzte Übertragung der therapeutischen Genkonstrukte in den Defekt ist wünschenswert. Gegenwärtige Strategien sind bestrebt, Signalwege der Knorpelheilung im Defekt zu modulieren. Sie umfassen entweder die Anregung der Zellproliferation, -reifung und der Matrixsynthese über einen direkten Transfer oder durch die Methode der Zelltransplantation. Unter den meistuntersuchten Kandidaten sind es die Polypeptidwachstumfaktoren, die die strukturelle Qualität des Reparaturgewebes verbessert haben. Erst ein besseres Verständnis der grundlegenden wissenschaftlichen Aspekte der Knorpeldefektreparatur, zusammen mit der Identifizierung von zusätzlichen molekularen Zielen und der Entwicklung von verbesserten Gentransfertechniken, kann eine klinische Anwendung der Gentherapie für Knorpeldefekte erlauben. Die ersten experimentellen Ergebnisse geben Anlass zu vorsichtigem Optimismus.

Abstract

Recent advances in gene transfer technology have provided novel tools for its therapeutic use in the regeneration of focal articular cartilage defects. Current strategies aiming at improving chondrogenic pathways in the new repair tissue that fills such defects include the stimulation of chondrocyte proliferation and maturation as well as the stimulation of matrix synthesis via direct or ex vivo approaches. To target gene vectors to cartilage defects, a localized intraarticular delivery into the defect of therapeutic gene constructs is necessary. This review outlines the basic scientific aspects of cartilage defect repair, defines the regenerative options that might be applied, summarizes the progress that has been made to date, and analyses some of the unique obstacles that need to be resolved before a clinical translation of gene therapy for cartilage defects may be considered.

Schlüsselwörter

Gentherapie - Knorpelschaden - Wachstumsfaktoren

Key words

gene therapy - cartilage defects - growth factors

Literatur

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