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Vergleich der Genexpressionsmuster humaner Chondrozyten und chondrogen differenzierter mesenchymaler Stammzellen für das Tissue-Engineering

A comparison of the gene expression patterns of human chondrocytes and chondrogen differentiated mesenchymal stem cells for tissue engineering

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Zusammenfassung

Hintergrund

Tissue-Engineering stellt eine vielversprechende Methode zur Herstellung autologer Knorpeltransplantate für die rekonstruktive Chirurgie dar. Ein Problem hierbei ist die Dedifferenzierung der Chondrozyten.

Methoden

In der vorliegenden Studie wurde die Genexpression verschiedener Marker einerseits während der Dedifferenzierung humaner Chondrozyten (HC) aus Septumknorpel und andererseits während der chondrogenen Differenzierung von mesenchymalen Stammzellen (hMSC) aus Knochenmarkproben in Zellkultur mittels Microarrays analysiert.

Ergebnisse

Kollagen 1α1, 2α1, 3α1, 4α1, 11α1, Biglykan, Fibromodulin und Lumican wurden während der Dedifferenzierung der HC aktiviert, Kollagen 9α2, 9α3, 10α1 und Chondroadherin inaktiviert. Während der chondrogenen Differenzierung der MSC wurden die Gene für Kollagen 3α1, 9α2, 9α3, 10α1, 11α1 aktiviert, die für Kollagen 4α1 und Fibromodulin inaktiviert, sowie die Gene für Col 1α1, Biglykan und Chondroadherin konstant exprimiert.

Schlussfolgerung

Das Genprofil von chondrogen differenzierten Stammzellen entspricht hinsichtlich der untersuchten Marker dem von humanen differenzierten Chondrozyten. Kollagen 2α1, 9α2, 9α3, 10α1 könnten Marker für die Differenzierung von Knorpelgewebe sein, Col 1α1, 3α1 und 4α1, Biglykan, Fibromodulin und Lumican für die Dedifferenzierung.

Abstract

Background

Tissue engineering is a promising method for the generation of chondrogenic grafts for reconstructive surgery. In cultured chondrocytes, the dedifferentiation of cells seems unavoidable for multiplication.

Methods

In this study, we investigated the expression of distinct markers during the dedifferentiation of human chondrocytes (HC) harvested during septoplasty and human mesenchymal stem cells (hMSC) from cartilage biopsies in cell culture using the microarray technique.

Results

The genes for collagen 1α1, 2α1, 3α1, 4α1, 11α1, biglycan, fibromodulin and lumican were activated during the dedifferentiation of the HCs, collagen 9α2, 9α3, 10α1 and chondroadherin were inactivated. During chondrogenic differentiation of hMSCs, the genes for collagen 3α1, 9α2, 9α3, 10α1, 11α1 were activated, collagen 4α1 and fibromodulin inactivated and the genes for Col 1α1, biglycan und chondroadherin constantly expressed.

Conclusion

The genetic profile for the investigated markers in human chondrocytes generated from hMSCs resembles the profile in differentiated chondrocytes. Collagen 2α1, 9α2, 9α3, 10α1 could represent markers for the differentiation of chondrocytes, Col 1α1, 3α1 und 4α1, biglycan, fibromodulin and lumican markers for the dedifferentiation into a more fibroblastoid cell type.

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Danksagung

Diese Untersuchung wurde gefördert durch einen „research grant“ (Nr 932817) der Fakultät für klinische Medizin Mannheim der Universität Heidelberg. Wir möchten Frau Petra Prohaska und Frau Susanne Kern für exzellente Unterstützung danken.

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Authors and Affiliations

  1. Universitäts-HNO-Klinik Mannheim

    U. R. Goessler, S. Bag, H. Sadick, K. Hörmann & F. Riedel

  2. Institut für Transfusionsmedizin und Immunologie, Deutsches Rotes Kreuz — Blutspendedienst Baden-Württemberg/Hessen, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg

    P. Bugert, K. Bieback & H. Klüter

  3. Universitäts-HNO-Klinik Mannheim, Theodor-Kutzer-Ufer, 68135, Mannheim

    U. R. Goessler

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  1. U. R. Goessler
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  2. P. Bugert
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  4. S. Bag
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Correspondence to U. R. Goessler.

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Goessler, U.R., Bugert, P., Bieback, K. et al. Vergleich der Genexpressionsmuster humaner Chondrozyten und chondrogen differenzierter mesenchymaler Stammzellen für das Tissue-Engineering. HNO 54, 258–266 (2006). https://doi.org/10.1007/s00106-005-1322-2

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