title: Enhancement of wound healing by human multipotent stromal cell conditioned medium: the paracrine factors and p38 MAPK activation.
abstract: Wound healing can be improved by transplanting mesenchymal stem cells (MSCs). In this study, we have demonstrated the benefits of the conditioned medium derived from human MSCs (CM-MSC) in wound healing using an excisional wound model. CM-MSC accelerated wound closure with increased reepithelialization, cell infiltration, granulation formation, and angiogenesis. Notably, CM-MSC enhanced epithelial and endothelial cell migration, suggesting the contribution of increased cell migration to wound healing enhanced by CM-MSC. Cytokine array, ELISA analysis, and quantitative RT-PCR revealed high levels of IL-6 in CM-MSC. Moreover, IL-6 added to the preconditioned medium enhanced both cell migration and wound healing, and antibodies against IL-6 blocked the increase in cell motility and wound closure by CM-MSC. The IL-6 secretory pathway of MSCs was inhibited by SB203580, an inhibitor of p38 MAPK or siRNA against p38 MAPK, suggesting IL-6 secretion by MSCs is mediated through the activation of p38 MAPK. Inactivation of p38 MAPK also reduced the expression and production of IL-8 and CXCL1 by MSCs, both of which were also demonstrated to enhance cell migration and wound closure. Thus, our data suggest MSCs promote wound healing through releasing a repertoire of paracrine factors via activation of p38 MAPK, and the CM-MSC may be applied to enhance wound healing.
authors.affiliation: Institute of Oral Biology, Department of Dentistry, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Tu-Lai
authors.initials: TL
authors.lastname: Yew
authors.forename: Yeh-Ting
authors.initials: YT
authors.lastname: Hung
authors.forename: Hsin-Yang
authors.initials: HY
authors.lastname: Li
authors.forename: Hsin-Wei
authors.initials: HW
authors.lastname: Chen
authors.forename: Ling-Lan
authors.initials: LL
authors.lastname: Chen
authors.forename: Kuo-Shu
authors.initials: KS
authors.lastname: Tsai
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.forename: Kuan-Chong
authors.initials: KC
authors.lastname: Chao
authors.forename: Tung-Fu
authors.initials: TF
authors.lastname: Huang
authors.forename: Hen-Li
authors.initials: HL
authors.lastname: Chen
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Hung
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D002465:Cell Movement; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012867:Skin / Q000098:blood supply / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000906:Antibodies; D054360:Chemokine CXCL1; D017077:Culture Media, Conditioned; D007093:Imidazoles; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D011725:Pyridines; D034741:RNA, Small Interfering; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580