Stich Stefan, Haag Marion, Häupl Thomas, Sezer Orhan, Notter Michael, Kaps Christian, Sittinger Michael, Ringe Jochen
Tissue Engineering Laboratory and Berlin-Brandenburg Center for Regenerative Therapies, Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Berlin, Germany.
Cell Tissue Res. 2009 May;336(2):225-36. doi: 10.1007/s00441-009-0768-z. Epub 2009 Mar 19.
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-1alpha) 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.
原位组织工程是再生医学中一种很有前景的方法，它有可能使成体干细胞或祖细胞通过趋化作用被引导至组织缺损处，随后分化为周围的组织类型。间充质干细胞（MSC）是有吸引力的候选细胞。趋化因子如CXCL12（SDF-1α）可趋化MSC，但对于MSC趋化和迁移所涉及的分子过程知之甚少。在本研究中，通过全基因组微阵列分析研究了CXCL12对MSC的募集作用。在体外试验中测量了骨髓来源的MSC对CXCL12的剂量依赖性迁移潜力，在CXCL12浓度为1000 nM时记录到最大值。对用CXCL12刺激的MSC和未刺激的对照进行微阵列分析，显示有30个差异表达基因（24个被诱导，6个被抑制）。通路分析揭示了11个参与细胞运动和细胞因子 - 细胞因子受体相互作用的差异表达基因，包括趋化因子CXCL8和CCL26、白细胞抑制因子、分泌粒蛋白II和前列腺素内过氧化物合酶2等迁移诱导剂的基因。通过对选定基因的实时聚合酶链反应证实了这些结果。所获得的数据为细胞迁移趋化过程中涉及的分子机制提供了进一步的见解，并将CXCL12指定为再生治疗中原位募集的有前景的候选物。
