214 UPREGULATION OF A DISTINCT SET OF CHEMOKINES FOLLOWING CAVERNOUS NERVE INJURY IS RESPONSIBLE FOR RECRUITMENT OF ADIPOSE TISSUE-DERIVED STEM CELLS TOWARDS THE MAJOR PELVIC GANGLION

Abstract

You have accessJournal of UrologyStem Cell Research1 Apr 2012214 UPREGULATION OF A DISTINCT SET OF CHEMOKINES FOLLOWING CAVERNOUS NERVE INJURY IS RESPONSIBLE FOR RECRUITMENT OF ADIPOSE TISSUE-DERIVED STEM CELLS TOWARDS THE MAJOR PELVIC GANGLION Maarten Albersen, Joost Berkers, Philip Dekoninck, Jan Deprest, Dirk De Ridder, and Frank Van Der Aa Maarten AlbersenMaarten Albersen Leuven, Belgium More articles by this author , Joost BerkersJoost Berkers Leuven, Belgium More articles by this author , Philip DekoninckPhilip Dekoninck Leuven, Belgium More articles by this author , Jan DeprestJan Deprest Leuven, Belgium More articles by this author , Dirk De RidderDirk De Ridder Leuven, Belgium More articles by this author , and Frank Van Der AaFrank Van Der Aa Leuven, Belgium More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.267AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES 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). The interaction between chemokines and their receptors plays a major role in this process. The objectives of this study were to examine chemokine-expression in neuro-inflammation of the rat MPG following cavernous nerve injury (CNI), and to match these chemokines to genomic, structural and functional expression of chemokine receptors (CRs) in human ADSC. METHODS (MPG) Six male 12 weeks old Sprague Dawley rats underwent laparotomy and bilateral crush injury of the cavernous nerves. Six rats served as sham controls (laparotomy and periprostatic dissection only). Twenty-four hours after CNI, the MPGs were harvested; RNA was isolated and subjected to qPCR analysis in triplicate. (ADSC) Human ADSC were isolated from subcutaneous adipose tissue of 5 consenting donors. Cells were subjected to qPCR for all 21 known CRs. These results were validated by FACS and intracellular FACS. Migration of ADSC towards gradients of CCL2,19,28; CX3CL1, CXCL12 and XCL1 was assessed in-vitro in a chemotaxis assay. RESULTS (MPG) Twenty-four hours following CNI, neuro-inflammation was present in the rat MPG as illustrated by significant upregulation of TNFA. Crush injury further resulted in significant upregulation of the chemokines CCL2,28, CXCL12, CX3CL1 and XCL1. (ADSC) RNA for CRs CCR1,3,4,10; CX3CR1; CXCR4,6,7; XCR1; CCRL1,2 was detected by qPCR of ADSC. Validation by FACS at p5 showed low membranous CR expression, however, intracellular FACS indicated high expression of CCR4,10, CX3CR1 and XCR1 at p5, and modest expression of of all other 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). Cells migrated towards gradients of CCL2,28, XCL1 and CX3CL1, but not towards CCL19. The number of cells migrated towards CXCL12 was low. CONCLUSIONS CNI-related neuro-inflammation is accompanied by the expression of various chemokines. 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, CXCR4/7-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. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e89 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Maarten Albersen Leuven, Belgium More articles by this author Joost Berkers Leuven, Belgium More articles by this author Philip Dekoninck Leuven, Belgium More articles by this author Jan Deprest Leuven, Belgium More articles by this author Dirk De Ridder Leuven, Belgium More articles by this author Frank Van Der Aa Leuven, Belgium More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...