Enhancement of Wound Healing by Human Multipotent Stromal Cell Conditioned Medium: The Paracrine Factors and p38 MAPK Activation
Autor: | Hen Li Chen, Tung Fu Huang, Hsin Wei Chen, Yeh Ting Hung, Tu Lai Yew, Ling Lan Chen, Kuo Shu Tsai, Hsin Yang Li, Shih-Chieh Hung, Kuan Chong Chao, Shih Hwa Chiou |
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Rok vydání: | 2011 |
Předmět: |
Pyridines
Angiogenesis Chemokine CXCL1 medicine.medical_treatment Biomedical Engineering Neovascularization Physiologic lcsh:Medicine Mesenchymal Stem Cell Transplantation p38 Mitogen-Activated Protein Kinases Antibodies Mice Paracrine signalling Cell Movement medicine Animals Humans RNA Small Interfering Cells Cultured Skin Mice Inbred BALB C Wound Healing Transplantation integumentary system Interleukin-6 Chemistry Interleukin-8 lcsh:R Mesenchymal stem cell Imidazoles Mesenchymal Stem Cells Cell migration Cell Biology Cell biology Enzyme Activation Endothelial stem cell CXCL1 Cytokine Culture Media Conditioned Intercellular Signaling Peptides and Proteins RNA Interference Wound healing |
Zdroj: | Cell Transplantation, Vol 20 (2011) |
ISSN: | 1555-3892 0963-6897 |
DOI: | 10.3727/096368910x550198 |
Popis: | 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. |
Databáze: | OpenAIRE |
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