title: Recruitment of mesenchymal stem cells and macrophages by dual release of stromal cell-derived factor-1 and a macrophage recruitment agent enhances wound closure.
abstract: In this study, the wound closure of mouse skin defects was examined in terms of recruitment of mesenchymal stem cells (MSC) and macrophages. For the cells recruitment, stromal derived factor-1 (SDF-1) of a MSC recruitment agent and sphingosine-1 phosphate agonist (SEW2871) of a macrophages recruitment agent were incorporated into gelatin hydrogels, and then released in a controlled fashion. When applied to a skin wound defect of mice, gelatin hydrogels incorporating mixed 500 ng SDF-1 and 0.4, 0.8, or 1.6 mg SEW2871-micelles recruited a higher number of both MSC and macrophages than those incorporating SDF-1 or phosphate buffered saline. However, the number of M1 phenotype macrophages for the hydrogel incorporating mixed SDF-1 and SEW2871-micelles recruited was remarkably low to a significant extent compared with that for those hydrogel incorporating 0.4, 0.8, or 1.6 mg SEW2871-micelles. On the other hand, the number of M2 macrophages 3 days after the implantation of the hydrogels incorporating SDF-1 and 0.4 mg SEW2871-micelles significantly increased compared with that for other hydrogels. In vivo experiments revealed the hydrogels incorporating SDF-1 and 0.4 mg SEW2871-micelles promoted the wound closure of skin defect to a significant stronger extent than those incorporating SEW2871-micelles, SDF-1, and a mixture of SDF-1 and higher doses of SEW2871-micelles. It is concluded that the in vivo recruitment of MSC and macrophages to the defects may contribute to the tissue regeneration of skin wound.
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-Cho Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan.
authors.forename: Yang-Hee
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-Cho Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
mesh_terms: D000818:Animals; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000008:administration & dosage* / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry*; D005780:Gelatin / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry; D008246:Lysophospholipids / Q000819:agonists; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D010069:Oxadiazoles / Q000008:administration & dosage* / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000293:injuries; D013110:Sphingosine / Q000819:agonists / Q000031:analogs & derivatives; D013552:Swine; D013876:Thiophenes / Q000008:administration & dosage* / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D054377:Chemokine CXCL12; D003692:Delayed-Action Preparations; D020100:Hydrogels; D008246:Lysophospholipids; D010069:Oxadiazoles; C503964:SEW2871; D013876:Thiophenes; C060506:sphingosine 1-phosphate; D005780:Gelatin; D013110:Sphingosine
keywords: MSC; cell recruitment; gelatin hydrogel; macrophage; wound closure