Release Of Stromal Cell-derived Factor-1 Research Articles

Controlled Release of Stromal-Cell-Derived Factor-1 from Gelatin Hydrogels Enhances Angiogenesis

Controlled release of a chemokine, stromal-cell-derived factor-1 (SDF-1), could be achieved with gelatin hydrogels of release carrier. Gelatin was chemically derivatized to give it different electric charge and hydrophobicity. Among the derivatives, succinylated gelatin (Succ) of an anionic charge was the most suitable for preparation of the hydrogel in terms of SDF-1 release. The time profile of SDF-1 release from the hydrogel of succinylated gelatin could be controlled by changing the water content of hydrogel which could be modified by changing the conditions of hydrogel preparation. When evaluated after the subcutaneous implantation of Succ hydrogels incorporating SDF-1 or injection of SDF-1 solution, significantly stronger angiogenesis by the hydrogel was observed. The hydrogel implantation also enhanced the mRNA level of SDF-1 receptor at the site implanted. It is possible that the gelatin hydrogel enabled SDF-1 to be released locally, resulting in an enhanced angiogenesis at the site implanted.

Localized and Sustained SDF-1 Gene Release Mediated by Fibronectin Films: A Potential Method for Recruiting Stem Cells

Gene-activated matrix has wide potential utilization in tissue engineering. It may genetically modify cells with plasmid DNA encoding therapeutic genes and allow sustained expression and release of the proteins to surrounding tissues. In this study, we assessed the feasibility of the local gene release from human fibronectin (HFN) substrate and the efficacy of local release of stromal cell-derived factor-1 (SDF-1) gene on c-kit+ cell homing. Cationic polymer polyethylenimine (25kDa PEI) was used as non-viral DNA vector. Gene-activated HFN (GAH) was prepared by mixing PEI/DNA complexes with HFN substrate. The DNA retardation, the complex size, and the DNA release speed from the GAH were studied. The in vitro transfection was optimized by luciferase expression and cell viability assay in the COS7 cell line. Localized gene expression in COS7 cells cultured on the GAH was assessed by LacZ and GFP-N3-SDF-1 marker genes. Ckit+ cell homing was investigated in response to the local in vitro SDF-1 expression from rat mesenchymal stem cells (RMSCs) cultured on GAH. Results showed GAH allows long time-sustained DNA release, localized gene delivery, and high transfection efficiency. Local SDF-1 expression with GAH is a promising method to induce targetable stem cell homing.

17β-Estradiol Promotes Breast Cancer Cell Proliferation-Inducing Stromal Cell-Derived Factor-1-Mediated Epidermal Growth Factor Receptor Transactivation: Reversal by Gefitinib Pretreatment

The coordinated activity of estrogens and epidermal growth factor receptor (EGFR) family agonists represents the main determinant of breast cancer cell proliferation. Stromal cell-derived factor-1 (SDF-1) enhances extracellular signal-regulated kinases 1 and 2 (ERK1/2) activity via the transactivation of EGFR and 17beta-estradiol (E2) induces SDF-1 production to exert autocrine proliferative effects. On this basis, we evaluated whether the inhibition of the tyrosine kinase (TK) activity of EGFR may control different mitogenic stimuli in breast tumors using the EGFR-TK inhibitor gefitinib to antagonize the proliferation induced by E2 in T47D human breast cancer cells. EGF, E2, and SDF-1 induced a dose-dependent T47D cell proliferation, that being nonadditive suggested the activation of common intracellular pathways. Gefitinib treatment inhibited not only the EGF-dependent proliferation and ERK1/2 activation but also the effects of SDF-1 and E2, suggesting that these activities were mediated by EGFR transactivation. Indeed, both SDF-1 and E2 caused EGFR tyrosine phosphorylation. The molecular link between E2 and SDF-1 proliferative effects was identified because 1,1'-(1,4-phenylenebis(methylene))-bis-1,4,8,11-tetraazacyclotetradecane octahydrochloride (AMD3100), a CXCR4 antagonist, inhibited SDF-1- and E2-dependent proliferation and EGFR and ERK1/2 phosphorylation. EGFR transactivation was dependent on c-Src activation. E2 treatment caused a powerful SDF-1 release from T47D cells. Finally, in SKBR3, E2-resistant cells, EGFR was constitutively activated, and AMD3100 reduced EGFR phosphorylation and cell proliferation, whereas HER2-neu was transactivated by SDF-1 in SKBR3 but not in T47D cells. In conclusion, we show that activation of CXCR4 transduces proliferative signals from the E2 receptor to EGFR, whose inhibition is able to revert breast cancer cell proliferation induced by multiple receptor activation.

Editorial: Tissue Engineering: Perspectives, Challenges, and Future Directions

Editorial: Tissue Engineering: Perspectives, Challenges, and Future Directions