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Open Access Highly Accessed Research article

Gene expression profiling of human mesenchymal stem cells derived from bone marrow during expansion and osteoblast differentiation

Birgit Kulterer1, Gerald Friedl2, Anita Jandrositz3, Fatima Sanchez-Cabo1, Andreas Prokesch1, Christine Paar1, Marcel Scheideler1, Reinhard Windhager2, Karl-Heinz Preisegger3 and Zlatko Trajanoski1*

Author Affiliations

1 Institute for Genomics and Bioinformatics and Christian-Doppler Laboratory for Genomics and Bioinformatics, Graz University of Technology, Graz, Austria

2 Department of Orthopaedics, Medical University of Graz, Graz, Austria

3 Eccocell Biotechnology Inc., Graz, Austria

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BMC Genomics 2007, 8:70  doi:10.1186/1471-2164-8-70

Published: 12 March 2007

Abstract

Background

Human mesenchymal stem cells (MSC) with the capacity to differentiate into osteoblasts provide potential for the development of novel treatment strategies, such as improved healing of large bone defects. However, their low frequency in bone marrow necessitate ex vivo expansion for further clinical application. In this study we asked if MSC are developing in an aberrant or unwanted way during ex vivo long-term cultivation and if artificial cultivation conditions exert any influence on their stem cell maintenance. To address this question we first developed human oligonucleotide microarrays with 30.000 elements and then performed large-scale expression profiling of long-term expanded MSC and MSC during differentiation into osteoblasts.

Results

The results showed that MSC did not alter their osteogenic differentiation capacity, surface marker profile, and the expression profiles of MSC during expansion. Microarray analysis of MSC during osteogenic differentiation identified three candidate genes for further examination and functional analysis: ID4, CRYAB, and SORT1. Additionally, we were able to reconstruct the three developmental phases during osteoblast differentiation: proliferation, matrix maturation, and mineralization, and illustrate the activation of the SMAD signaling pathways by TGF-β2 and BMPs.

Conclusion

With a variety of assays we could show that MSC represent a cell population which can be expanded for therapeutic applications.