title: Ex vivo microperfusion system of the adipose organ: a new approach to studying the mobilization of adipose cell populations.
abstract: OBJECTIVE
  Adipose tissue (AT) is a dynamic organ that expands and contracts rapidly. It is composed of adipocytes and of cell populations among which immune cells and mesenchymal progenitors known as adipose stromal cells (ASCs). The AT cell turnover has been extensively studied. Surprisingly it has only been viewed as the result of both cell proliferation/death and cell infiltration. Nevertheless, both immune cells and ASCs exhibit migration abilities; therefore their egress from AT in response to physiological/pathophysiological stimuli has to be considered. To do so, the aim of the present work was to develop a model allowing the study of cell release from the adipose organ.
  
  
  METHODS
  Mesenteric (Mes) ATs were isolated from 9-week-old C57BL/6 male mice and were catheterized via the superior mesenteric artery and were perfused with a saline solution. After an equilibration period, the mesenteric fat pad was perfused with CXCL12 (stromal-derived factor-1, SDF-1) or sphingosine 1-phosphate (S1P) to trigger cell mobilization and perfusates were collected every 30 min for subsequent flow cytometry analyses.
  
  
  RESULTS
  We report here that CXCL12 induces the specific release of ASCs from MesAT thus demonstrating that ASCs are specifically mobilized from fat depots by a CXCL12-dependent pathway. Moreover, we showed that leukocyte mobilization can be triggered via a S1P-dependent pathway.
  
  
  CONCLUSIONS
  We have developed a microperfusion model of an intact fat depot allowing the study of AT cell release in response to various molecules. The perfusion system described here demonstrates that ASCs and leukocytes can be pharmacologically mobilized from AT. Therefore, AT microperfusion might constitute an appropriate and reliable approach for evaluating the mobilization of different cell populations from AT in various physiological and pathophysiological contexts. Such a model might help in identifying factors and drugs controlling AT cell release, impacting the medical fields of regenerative medicine and of obesity or its associated comorbidities.
authors.affiliation: 1] Inserm U1031 STROMAlab BP 84 225-F-31 432, Toulouse, France [2] CNRS, Université Toulouse III, UPS UMR5273 STROMAlab, BP 84 225-F-31 432, Toulouse, France [3] EFS (Etablissement Français du Sang), STROMAlab BP 84 225-F-31 432, Toulouse, France [4] Université Toulouse III, UPS UMR5273 STROMAlab BP 84 225-F-31 432, Toulouse, France.
authors.forename: M
authors.initials: M
authors.lastname: Gil-Ortega
authors.affiliation: Instituto Pluridisciplinar, Facultad de Farmacia, Universidad Complutense de Madrid, Juan XXIII 1, 28040 Madrid, Spain.
authors.forename: M S
authors.initials: MS
authors.lastname: Fernández-Alfonso
authors.affiliation: Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, 28668 Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Somoza
authors.affiliation: 1] Inserm U1031 STROMAlab BP 84 225-F-31 432, Toulouse, France [2] CNRS, Université Toulouse III, UPS UMR5273 STROMAlab, BP 84 225-F-31 432, Toulouse, France [3] EFS (Etablissement Français du Sang), STROMAlab BP 84 225-F-31 432, Toulouse, France [4] Université Toulouse III, UPS UMR5273 STROMAlab BP 84 225-F-31 432, Toulouse, France.
authors.forename: L
authors.initials: L
authors.lastname: Casteilla
authors.affiliation: 1] Inserm U1031 STROMAlab BP 84 225-F-31 432, Toulouse, France [2] CNRS, Université Toulouse III, UPS UMR5273 STROMAlab, BP 84 225-F-31 432, Toulouse, France [3] EFS (Etablissement Français du Sang), STROMAlab BP 84 225-F-31 432, Toulouse, France [4] Université Toulouse III, UPS UMR5273 STROMAlab BP 84 225-F-31 432, Toulouse, France.
authors.forename: C
authors.initials: C
authors.lastname: Sengenès
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D007150:Immunohistochemistry; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D008643:Mesentery / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D010477:Perfusion; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine