title: SCF increases in utero-labeled stem cells migration and improves wound healing.
abstract: Diabetic skin wounds lack the ability to heal properly and constitute a major and significant complication of diabetes. Nontraumatic lower extremity amputations are the number one complication of diabetic skin wounds. The complexity of their pathophysiology requires an intervention at many levels to enhance healing and wound closure. Stem cells are a promising treatment for diabetic skin wounds as they have the ability to correct abnormal healing. Stem cell factor (SCF), a chemokine expressed in the skin, can induce stem cells migration, however the role of SCF in diabetic skin wound healing is still unknown. We hypothesize that SCF would correct the impairment and promote the healing of diabetic skin wounds. Our results show that SCF improved wound closure in diabetic mice and increased HIF-1α and vascular endothelial growth factor (VEGF) expression levels in these wounds. SCF treatment also enhanced the migration of red fluorescent protein (RFP)-labeled skin stem cells via in utero intra-amniotic injection of lenti-RFP at E8. Interestingly these RFP+ cells are present in the epidermis, stain negative for K15, and appear to be distinct from the already known hair follicle stem cells. These results demonstrate that SCF improves diabetic wound healing in part by increasing the recruitment of a unique stem cell population present in the skin.
authors.affiliation: Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver, Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado.
authors.forename: Carlos
authors.initials: C
authors.lastname: Zgheib
authors.affiliation: Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver, Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado.
authors.forename: Junwang
authors.initials: J
authors.lastname: Xu
authors.affiliation: University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Mallette
authors.affiliation: University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Caskey
authors.affiliation: University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver, Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado.
authors.forename: Junyi
authors.initials: J
authors.lastname: Hu
authors.affiliation: Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver, Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Liechty
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000502:physiology; D003921:Diabetes Mellitus, Experimental; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D053569:Keratin-15 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D011247:Pregnancy; D011270:Pregnancy, Animal; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000196:embryology / Q000293:injuries* / Q000378:metabolism; D019089:Stem Cell Factor / Q000096:biosynthesis / Q000235:genetics*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D014945:Wound Healing / Q000235:genetics*; D014947:Wounds and Injuries / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D053569:Keratin-15; C492053:Krt15 protein, mouse; D019089:Stem Cell Factor; D012313:RNA