title: The role of SDF-1 in homing of human adipose-derived stem cells.
abstract: One of the putative pathophysiological mechanisms of chronic wounds is a disturbed homing of stem cells. In this project, the stromal cell-derived factor 1 (SDF-1)/C-X-C chemokine receptor (CXCR) 4 and SDF-1/CXCR7 pathway were focused in human adipose-derived stem cells (ASCs). ASCs were incubated with acute (AWF) or chronic wound fluid (CWF) to analyze their effects by quantitative real-time polymerase chain reaction (SDF-1, CXCR4, CXCR7, TIMP3), enzyme-linked immunosorbent assay (SDF-1 in WFs and supernatant), and transwell migration assay with/without antagonization. Whereas SDF-1 amounted 73.5 pg/mL in AWF, it could not be detected in CWF. Incubation with AWF led to a significant enhancement (129.7 pg/mL vs. 95.5 pg/mL), whereas CWF resulted in a significant reduction (30 pg/mL vs. 95.5 pg/mL) of SDF-1 in ASC supernatant. The SDF-1 receptor CXCR7 was detected on ASCs. AWF but not CWF significantly induced ASC migration, which was inhibited by CXCR4 and CXCR7 antagonists. Expressions of SDF-1, CXCR4, and CXCR7 were significantly stimulated by AWF while TIMP3 expression was reduced. In conclusion, an uncontrolled inflammation in the chronic wound environment, indicated by a reduced SDF-1 expression, resulted in a decreased ASC migration. A disturbed SDF-1/CXCR4 as well as SDF-1/CXCR7 pathway seems to play an important role in the impaired healing of chronic wounds.
authors.affiliation: Institute for Research in Operative Medicine (IFOM), University of Witten/Herdecke, Cologne, Germany.
authors.forename: Ewa K
authors.initials: EK
authors.lastname: Stuermer
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lipenksy
authors.forename: Oliver
authors.initials: O
authors.lastname: Thamm
authors.forename: Edmund
authors.initials: E
authors.lastname: Neugebauer
authors.forename: Nadine
authors.initials: N
authors.lastname: Schaefer
authors.forename: Paul
authors.initials: P
authors.lastname: Fuchs
authors.forename: Bertil
authors.initials: B
authors.lastname: Bouillon
authors.forename: Paola
authors.initials: P
authors.lastname: Koenen
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D054387:Receptors, CXCR / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012883:Skin Ulcer / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014019:Tissue Donors; D014945:Wound Healing
chemical_list: C501896:ACKR3 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D019718:Receptors, CXCR4