Title: Genomic, structural and functional expression of a distinct set of chemokine-receptors may be responsible for homing of adipose tissue-derived stem cells towards the major pelvic ganglion following cavernous nerve injury
Authors: Albersen, Maarten
DeKoninck, Philip
Berkers, Joost
Van Haute, Carl
Zia, Silvia
Deprest, Jan
De Ridder, Dirk
Van der Aa, Frank #
Issue Date: Dec-2011
Publisher: Wiley-blackwell
Host Document: Journal of sexual medicine vol:8 pages:407-407
Conference: Congress of the European Society for Sexual Medecine edition:15 location:Amsterdam date:6 - 9 December 2011
Abstract: Objective
We have recently demonstrated the essential role of adipose tissue-derived stem cell (ADSC) recruitment towards the major pelvic ganglion (MPG) in rats following cavernous nerve injury (CNI). We showed upregulation of the chemokines CCL2,22,28, CXCL12, CX3CL1 and XCL1 in the MPG following CNI. The objective of this study was to examine chemokine receptor (CR) expression in human ADSC to identify chemokines and their receptors responsible for this migratory process.
Human ADSC were isolated from subcutaneous adipose tissue of 5 consenting donors. ADSC were cultured up till passage 5 (p5) and characterized by FACS and differentiation potential towards adipogenic and osteogenic lineages. Cells were subjected to qPCR for all 21 known CRs. These results were validated by FACS and intracellular FACS. Functional activation of CR in ADSC was tested with CCL2,11,19,28; CX3CL1, XCXL12 and XCL1 by calcium-imaging and controlled by actin polymerization assay.
RNA for CRs CCR1,3,4,10; CX3CR1; CXCR4,6,7; XCR1; CCRL1,2 was detected by qPCR at p5. Validation by FACS at p5 showed very low membranous CR expression, however, intracellular FACS indicated high expression of CCR4,10, CX3CR1; CXCR6,7 and XCR1 at p5, and of all qPCR-detected CRs except CCRL1 and 2. Functional activation by calcium imaging was present for CCL2 (binds to CCR4), CCL28 (CCR10), CX3CL1 (CX3CR1) and XCL1 (XCR1). Responses were more pronounced at p0 than at p5. CCL11 (CCR3) evoked insignificant responses, and CCL19 (CCR7) did not induce calcium influx. These results were corroborated by an actin polymerization assay under fluorescence microscopy.
We identified the ligand-CR pairs CCL2-CCR4, CCL28-CCR10, CX3CL1-CX3CR1 and XCL1-XCR1 as potentially responsible for ADSC homing towards the MPG following CNI. Surprisingly, CXCR4-SDF1(CXCL12), is not likely a major homing factor for ADSC, as previously proposed. Modification of expression of these receptors in ADSC could improve homing and thus treatment efficacy.
ISSN: 1743-6095
Publication status: published
KU Leuven publication type: IMa
Appears in Collections:Centre for Surgical Technologies
Translational Cell & Tissue Research
# (joint) last author

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