Mesenchymal stem cells induce dermal fibroblast responses to injury.
Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. When co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury.
Smith
Andria N
AN
University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104, USA. snosmith@u.washington.edu
Willis
Elise
E
Chan
Vincent T
VT
Muffley
Lara A
LA
Isik
F Frank
FF
Gibran
Nicole S
NS
Hocking
Anne M
AM
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D020405:Dermis / Q000166:cytology*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D015870:Gene Expression / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D053507:Matrix Metalloproteinase 11 / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019899:Paracrine Communication / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D015703:Antigens, CD; D017077:Culture Media, Conditioned; D039001:Integrin alpha Chains; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1; C085725:integrin alpha7; D018799:Intercellular Adhesion Molecule-1; C511771:MMP11 protein, human; D053507:Matrix Metalloproteinase 11