The role of SDF-1 in homing of human adipose-derived stem cells

TY - JOUR

T1 - The role of SDF-1 in homing of human adipose-derived stem cells

AU - Stuermer, Ewa K

AU - Lipenksy, Alexandra

AU - Thamm, Oliver

AU - Neugebauer, Edmund

AU - Schaefer, Nadine

AU - Fuchs, Paul

AU - Bouillon, Bertil

AU - Koenen, Paola

N1 - © 2015 by the Wound Healing Society.

PY - 2015/1/13

Y1 - 2015/1/13

N2 - 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.

AB - 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.

KW - Adipose Tissue/cytology

KW - Cell Movement

KW - Cell Proliferation

KW - Chemokine CXCL12/metabolism

KW - Chronic Disease

KW - Enzyme-Linked Immunosorbent Assay

KW - Humans

KW - Mesenchymal Stem Cells/metabolism

KW - Receptors, CXCR/antagonists & inhibitors

KW - Receptors, CXCR4/metabolism

KW - Skin Ulcer/metabolism

KW - Tissue Donors

KW - Wound Healing

U2 - 10.1111/wrr.12248

DO - 10.1111/wrr.12248

M3 - SCORING: Journal article

C2 - 25581571

VL - 23

SP - 82

EP - 89

JO - WOUND REPAIR REGEN

JF - WOUND REPAIR REGEN

SN - 1067-1927

IS - 1

ER -