title: Directed cell migration via chemoattractants released from degradable microspheres.
abstract: Chemotaxis, cell migration directed by spatial concentration gradients of chemoattractant molecules, is critical for proper function of the immune system. Materials capable of generating defined chemoattractant gradients via controlled release may be useful for the design of improved vaccines and immunotherapies that draw specific cells to an immunization site. To this end, we encapsulated formyl-Nle-Leu-Phe-Nle-Tyr-Lys (fN'LFN'YK) peptides or macrophage inflammatory protein-3alpha (MIP-3alpha or CCL20) in degradable poly(lactide-co-glycolide) microspheres that provided sustained release for more than 2 weeks in vitro. fN'LFN'YK and MIP-3alpha chemoattract dendritic cells (DCs), the key antigen-presenting cells involved in generation of primary immune responses, and their precursors, monocytes. Using an in vitro videomicroscopy migration assay, we detected strong chemotaxis of human monocytes and monocyte-derived DCs through 3D collagen gels toward microspheres releasing fN'LFN'YK. Similarly, microparticles releasing MIP-3alpha were able to attract mouse bone marrow-derived dendritic cells. Strikingly, prolonged attraction of DCs from distances up to 500 microm from the source to the point of contact with individual microspheres was observed. Such microspheres could be of general interest for the design of vaccines that promote adaptive immunity and as a platform for studying the biology of chemotaxis in vitro and in vivo.
authors.affiliation: Department of Materials Science & Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhao
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Jain
authors.forename: H
authors.initials: H
authors.lastname: Benjamin Larman
authors.forename: Sandra
authors.initials: S
authors.lastname: Gonzalez
authors.forename: Darrell John
authors.initials: DJ
authors.lastname: Irvine
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000008:administration & dosage / Q000737:chemistry; D002630:Chemotactic Factors / Q000008:administration & dosage* / Q000737:chemistry*; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D004058:Diffusion; D006801:Humans; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry; D019402:Macrophage Inflammatory Proteins / Q000008:administration & dosage / Q000737:chemistry; D008422:Materials Testing; D051379:Mice; D008863:Microspheres; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry
chemical_list: C108355:CCL20 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D002630:Chemotactic Factors; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D019402:Macrophage Inflammatory Proteins; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid