title: Forearm ischemia decreases endothelial colony-forming cell angiogenic potential.
abstract: OBJECTIVE
  Circulating endothelial progenitor cells and especially endothelial colony-forming cells (ECFCs) are promising candidate cells for endothelial regenerative medicine of ischemic diseases, but the conditions for an optimal collection from adult blood must be improved.
  
  
  METHODS
  On the basis of a recently reported vascular niche of ECFCs, we hypothesized that a local ischemia could trigger ECFC mobilization from the vascular wall into peripheral blood to optimize their collection for autologous implantation in critical leg ischemia. Because the target population with critical leg ischemia is composed of elderly patients in whom a vascular impairment has been documented, we also analyzed the impact of aging on ECFC mobilization and vascular integrity.
  
  
  RESULTS
  After having defined optimized ECFC culture conditions, we studied the effect of forearm ischemia on ECFC numbers and functions in 26 healthy volunteers (13 volunteers ages 20-30-years old versus 13 volunteers ages 60-70 years old). The results show that forearm ischemia induced an efficient local ischemia and a normal endothelial response but did not mobilize ECFCs regardless of the age group. Moreover, we report an alteration of angiogenic properties of ECFCs obtained after forearm ischemia, in vitro as well as in vivo in a hindlimb ischemia murine model. This impaired ECFC angiogenic potential was not associated with a quantitative modification of the circulating endothelial compartment.
  
  
  CONCLUSIONS
  The procedure of local ischemia, although reulting in a preserved endothelial reactivity, did not mobilize ECFCs but altered their angiogenic potential.
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cite, Paris, France; Inserm UMR_S765, Faculté de Pharmacie, Paris, France; AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Mauge
authors.affiliation: Inserm UMR_S1076, Université de la Méditerranée, Faculté de Pharmacie, Marseille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Sabatier
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cite, Paris, France; Inserm UMR_S970, PARCC, Paris, France; AP-HP, Hôpital Européen Georges Pompidou, Service de Pharmacologie Clinique, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Boutouyrie
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cite, Paris, France; Inserm UMR_S765, Faculté de Pharmacie, Paris, France; AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France.
authors.forename: Clément
authors.initials: C
authors.lastname: D'Audigier
authors.affiliation: AP-HP, Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 9201, Paris, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Peyrard
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cite, Paris, France; Inserm UMR_S970, PARCC, Paris, France; AP-HP, Hôpital Européen Georges Pompidou, Service de Pharmacologie Clinique, Paris, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bozec
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cite, Paris, France; AP-HP, Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 9201, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Blanchard
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cite, Paris, France; AP-HP, Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 9201, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Azizi
authors.affiliation: Inserm UMR_S765, Faculté de Pharmacie, Paris, France.
authors.forename: Blandine
authors.initials: B
authors.lastname: Dizier
authors.affiliation: Inserm UMR_S1076, Université de la Méditerranée, Faculté de Pharmacie, Marseille, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cite, Paris, France; Inserm UMR_S765, Faculté de Pharmacie, Paris, France; AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Gaussem
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cite, Paris, France; Inserm UMR_S765, Faculté de Pharmacie, Paris, France; AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France. Electronic address: david.smadja@egp.aphp.fr.
authors.forename: David M
authors.initials: DM
authors.lastname: Smadja
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D005260:Female; D005542:Forearm / Q000098:blood supply / Q000503:physiopathology*; D006614:Hindlimb / Q000098:blood supply / Q000503:physiopathology*; D006801:Humans; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D033581:Stem Cell Transplantation; D013234:Stem Cells; D055815:Young Adult
keywords: aging; endothelial colony-forming cells; endothelial progenitor cells; forearm ischemia; mobilization