The International Journal of Biochemistry & Cell Biology 41 (2009) 649–658 Contents lists available at ScienceDirect The International Journal of Biochemistry & Cell Biology journal homepage: www.elsevier.com/locate/biocel Gene expression profile of adult human bone marrow-derived mesenchymal stem cells stimulated by the chemokine CXCL7 Gregor Kalwitz a , Michaela Endres a,b , Katja Neumann a , Karl Skriner c , Jochen Ringe b,e , Orhan Sezer d , Michael Sittinger b,e , Thomas Häupl c , Christian Kaps a,b,∗ a TransTissue Technologies GmbH, Tucholskystrasse 2, 10117 Berlin, Germany b Tissue Engineering Laboratory, Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Tucholskystrasse 2, 10117 Berlin, Germany c Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany d Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany e Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Tucholskystrasse 2, 10117 Berlin, Germany article info Article history: Received 21 April 2008 Received in revised form 21 July 2008 Accepted 21 July 2008 Available online 30 July 2008 Keywords: Mesenchymal stem cells Chemotaxis Chemokine Microarray Migration abstract A variety of chemokines has been shown to recruit human bone marrow-derived mesenchymal stem cells (MSC) and may be potential candidates for chemokine-based tissue regeneration approaches. The aim of our study was to determine whether the chemokine CXCL7 stimulates migration of human bone marrow-derived MSC and to analyze the effect of CXCL7 on the recruitment of MSC on the broad molec- ular level. Chemotaxis assays documented that high doses of CXCL7 significantly recruited MSC. Gene expression profiling using oligonucleotide microarrays showed that MSC treated with CXCL7 differentially expressed genes related to cell migration, cell adhesion and extracellular matrix remodeling. Pathway analysis showed that CXCL7 induced the expression of all chemokines binding the interleukin (IL) recep- tors A and B, CXCR1 and CXCR2, as well as the IL6 signal transducer (gp130) and its ligands IL6 and leukemia inhibitory factor (LIF). Induction of differentially expressed chemokines CXCL1-3, CXCL5, and CXCL6 as well as LIF and gp130 in MSC by CXCL7 was verified by real-time polymerase chain reaction. Immunoassay of cell culture supernatants confirmed elevated levels of the interleukins 6 and 8 in MSC upon treatment with CXCL7. Chemotaxis assays showed that interleukin 6 did not recruit MSC. In conclusion, CXCL7 sig- nificantly stimulates the migration of human MSC in vitro. Pathway analysis suggests that recruitment of human MSC by CXCL7 is supported by the induction of ligands of the interleukin 8 receptors, synergistically activating the respective signaling pathways. © 2008 Elsevier Ltd. All rights reserved. 1. Introduction Human mesenchymal stem cells (MSC) reside in a variety of adult tissues including bone marrow and are considered as attrac- tive progenitors for the regeneration of mesenchymal tissues in regenerative medicine (Barry and Murphy, 2004; Jorgensen et al., 2004; Ringe et al., 2002). Bone marrow-derived MSC can be grown in vitro, are suggested to remain undifferentiated when expanded extensively, but gradually loose their proliferation and differentia- tion capacity with an increasing number of cell passages (Mauney et al., 2005). MSC have the capacity to undergo various mesenchy- mal lineage development and have been shown to differentiate into bone, cartilage and fat cells (Pittenger et al., 1999). In regenerative ∗ Corresponding author at: TransTissue Technologies GmbH, Tucholskystrasse 2, 10117 Berlin, Germany. Tel.: +49 30 450 513 293; fax: +49 30 450 513 957. E-mail address: christian.kaps@transtissue.com (C. Kaps). medicine, clinical studies have been reported using in vitro prop- agated bone marrow-derived MSC for the restoration of articular cartilage surfaces in osteoarthritic lesions (Wakitani et al., 2002, 2004), for the regeneration of bone in maxillary sinus floor augmen- tation (Ueda et al., 2005) and for cardiovascular diseases (Giordano et al., 2007). Stem cell-based therapies require tissue biopsies and extensive manipulation of MSC. Thus, cell-based therapies may be stressful for the patient due to donor site morbidity and are time and labor consuming. Therefore, in situ approaches have been sug- gested that may rely on cell recruitment (Ringe et al., 2007) and in vivo maturation of MSC (Richter, 2007). Recruitment of MSC has been shown to be mediated by differ- ent growth factors like bone morphogenetic proteins, insulin like growth factors (Fiedler et al., 2006, 2002) as well as chemokines (Honczarenko et al., 2006; Sordi et al., 2005). Chemokines function as chemoattractants for e.g. leukocytes, while also exhibiting the ability to modulate for example angiogenesis, wound healing and tumorgenesis. Chemokines are a family of chemotactic cytokines 1357-2725/$ – see front matter © 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.biocel.2008.07.011