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Gene expression profiling of human mesenchymal stem cells chemotactically induced with CXCL12

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Abstract

In situ tissue engineering is a promising approach in regenerative medicine, with the possibility that adult stem or progenitor cells will be guided chemotactically to a tissue defect and subsequently differentiate into the surrounding tissue type. Mesenchymal stem cells (MSC) represent attractive candidate cells. Chemokines such as CXCL12 (SDF-1α) chemoattract MSC, but little is known about the molecular processes involved in the chemotaxis and migration of MSC. In this study, MSC recruitment by CXCL12 was investigated by genome-wide microarray analysis. The dose-dependent migration potential of bone-marrow-derived MSC toward CXCL12 was measured in an in vitro assay, with a maximum being recorded at a concentration of 1,000 nM CXCL12. Microarray analysis of MSC stimulated with CXCL12 and non-stimulated controls showed 30 differentially expressed genes (24 induced and six repressed). Pathway analysis revealed 11 differentially expressed genes involved in cellular movement and cytokine-cytokine receptor interaction, including those for migratory inducers such as the chemokines CXCL8 and CCL26, the leukocyte inhibitory factor, secretogranin II, and prostaglandin endoperoxide synthase 2. These results were confirmed by real-time polymerase chain reaction for selected genes. The obtained data provide further insights into the molecular mechanisms involved in chemotactic processes in cell migration and designate CXCL12 as a promising candidate for in situ recruitment in regenerative therapies.

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Acknowledgements

We thank Anja Wachtel and Samuel Vetterlein for excellent technical assistance.

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Authors and Affiliations

  1. Tissue Engineering Laboratory and Berlin-Brandenburg Center for Regenerative Therapies, Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Tucholskystrasse 2, 10117, Berlin, Germany

    Stefan Stich, Marion Haag, Thomas Häupl, Michael Sittinger & Jochen Ringe

  2. Department of Hematology and Oncology, Charité-University Medicine Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Orhan Sezer

  3. Department of Hematology and Oncology, Charité-University Medicine Berlin, Hindenburgdamm 30, 12200, Berlin, Germany

    Michael Notter

  4. TransTissue Technologies, Tucholskystrasse 2, 10117, Berlin, Germany

    Christian Kaps

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  1. Stefan Stich
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  2. Marion Haag
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  3. Thomas Häupl
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  4. Orhan Sezer
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  5. Michael Notter
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  6. Christian Kaps
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  7. Michael Sittinger
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  8. Jochen Ringe
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Corresponding author

Correspondence to Jochen Ringe.

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Stefan Stich and Marion Haag contributed equally to this work.

This study was supported by the Investitionsbank Berlin and the European Regional Development Fund (grant: 10128098), Deutsche Forschungsgemeinschaft (grant: DFG SI 569/7–1), and the Bundesministerium für Bildung und Forschung (Bioinside: 13N9817).

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Stich, S., Haag, M., Häupl, T. et al. Gene expression profiling of human mesenchymal stem cells chemotactically induced with CXCL12. Cell Tissue Res 336, 225–236 (2009). https://doi.org/10.1007/s00441-009-0768-z

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