title: Enhancement of wound healing by secretory factors of endothelial precursor cells derived from human embryonic stem cells.
abstract: OBJECTIVE
  Stem cells have been shown to have a therapeutic effect in several ischemic animal models, including hindlimb ischemia and chronic wound. We examined the wound-healing effect of secretory factors released by human embryonic stem cell (hESC)-derived endothelial precursor cells (EPC) in cutaneous excisional wound models.
  
  
  METHODS
  hESC-EPC were sorted by CD133/KDR, and endothelial characteristics were confirmed by reverse transcription (RT)-polymerase chain reaction (PCR), Matrigel assay and ac-LDL uptake. Conditioned medium (CM) of hESC-EPC was prepared, and concentrated hESC-EPC CM was applied in a mouse excisional wound model.
  
  
  RESULTS
  hESC-EPC CM accelerated wound healing and increased the tensile strength of wounds after topical treatment and subcutaneous injection. In addition, hESC-EPC CM treatment caused more rapid re-formation of granulation tissue and re-epithelialization of wounds compared with control vehicle medium and CB-EPC CM-treated wounds. In vitro, hESC-EPC CM significantly improved the proliferation and migration of dermal fibroblasts and epidermal keratinocytes. hESC-EPC CM also increased the extracellular matrix synthesis of fibroblasts. Analysis of hESC-EPC CM with a multiplex cytokine array system indicated that hESC-EPC secreted distinctively different cytokines and chemokines, such as epidermal growth factor (EGF), fibroblast growth factor (bFGF), fractalkine, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, IL-8, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor (VEGF), which are well known to be important in normal angiogenesis and wound healing.
  
  
  CONCLUSIONS
  This study has demonstrated the wound-healing effect of hESC-EPC CM and characterized the spectrum of cytokines released by hESC-EPC that are functionally involved in the wound-healing process. These results suggest that secretory factors released from stem cells could be an important mediator of stem cell therapy in ischemic tissue diseases.
authors.affiliation: Graduate School of Life Science, CHA Stem Cell Institute, College of Medicine, CHA University, Gangnam gu, Seoul, Korea.
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Lee
authors.forename: Jumi
authors.initials: J
authors.lastname: Kim
authors.forename: Kyung Il
authors.initials: KI
authors.lastname: Lee
authors.forename: Jeong Min
authors.initials: JM
authors.lastname: Shin
authors.forename: Jung Il
authors.initials: JI
authors.lastname: Chae
authors.forename: Hyung Min
authors.initials: HM
authors.lastname: Chung
mesh_terms: D000287:Administration, Topical; D000818:Animals; D049109:Cell Proliferation; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004817:Epidermis / Q000293:injuries; D005109:Extracellular Matrix / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007279:Injections, Subcutaneous; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D015603:Keratinocytes / Q000502:physiology; D051379:Mice; D014945:Wound Healing
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins