Laetitia Mauge1, Florence Sabatier2, Pierre Boutouyrie3, Clément D'Audigier1, Séverine Peyrard4, Erwan Bozec3, Anne Blanchard5, Michel Azizi5, Blandine Dizier6, Françoise Dignat-George2, Pascale Gaussem1, David M Smadja7. 1. 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. 2. Inserm UMR_S1076, Université de la Méditerranée, Faculté de Pharmacie, Marseille, France. 3. 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. 4. AP-HP, Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 9201, Paris, France. 5. Université Paris Descartes, Sorbonne Paris Cite, Paris, France; AP-HP, Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 9201, Paris, France. 6. Inserm UMR_S765, Faculté de Pharmacie, Paris, France. 7. 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.
Abstract
BACKGROUND AIMS: 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.
BACKGROUND AIMS: 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 ischemiamurine 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: David M Smadja; Juan M Melero-Martin; Jeroen Eikenboom; Mackenzie Bowman; Florence Sabatier; Anna M Randi Journal: J Thromb Haemost Date: 2019-05-22 Impact factor: 5.824
Authors: Elisa Rossi; Sonia Poirault-Chassac; Ivan Bieche; Richard Chocron; Anne Schnitzler; Anna Lokajczyk; Pierre Bourdoncle; Blandine Dizier; Nour C Bacha; Nicolas Gendron; Adeline Blandinieres; Coralie L Guerin; Pascale Gaussem; David M Smadja Journal: Stem Cell Rev Rep Date: 2019-08 Impact factor: 5.739
Authors: Dimitar Tasev; Michiel H van Wijhe; Ester M Weijers; Victor W M van Hinsbergh; Pieter Koolwijk Journal: PLoS One Date: 2015-06-15 Impact factor: 3.240