Stem Cell Reviews and Reports

, Volume 7, Issue 1, pp 208–220

Transplanted Late Outgrowth Endothelial Progenitor Cells as Cell Therapy Product for Stroke

  • Chahrazad Moubarik
  • Benjamin Guillet
  • Bennis Youssef
  • Jean-Laurent Codaccioni
  • Marie-Dominique Piercecchi
  • Florence Sabatier
  • Pellegrini Lionel
  • Laetitia Dou
  • Alexandrine Foucault-Bertaud
  • Lionel Velly
  • Françoise Dignat-George
  • Pascale Pisano
Article

DOI: 10.1007/s12015-010-9157-y

Cite this article as:
Moubarik, C., Guillet, B., Youssef, B. et al. Stem Cell Rev and Rep (2011) 7: 208. doi:10.1007/s12015-010-9157-y

Abstract

Endothelial progenitor cells (EPCs) seem to be a promising option to treat patients with ischemic diseases. Here, we investigated the effects of late outgrowth EPCs, or endothelial colony-forming cells (ECFCs), a recently defined homogeneous subtype of EPCs, in a rat model of transient middle cerebral artery occlusion (MCAO). Either vehicle or 4.106 ECFCs, isolated from human cord blood, were intravenously injected 24 h after 1 h MCAO in rats assigned to control and transplanted groups respectively. 111In-oxine-labeled ECFCs specifically homed to ischemic hemisphere and CM-Dil prelabeled ECFCs preferentially settled in the inner boundary of the core area of transplanted animals. Although incorporation of cells into neovessels was hardly detectable, ECFCs transplantation was associated with a reduction in apoptotic cell number, an increase in capillary density and a stimulation of neurogenesis at the site of injury. These effects were associated with an increase in growth factors expression in homogenates from ischemic area and may be related to the secretion by ECFCs of soluble factors that could affect apoptosis, vascular growth and neurogenesis. Microscopic examination of the ischemic hemisphere showed that ECFCs transplantation was also associated with a reduction in reactive astrogliosis. In conclusion, we demonstrated that ECFCs injected 24 h after MCAO settled in the injured area and improved functional recovery. The neurological benefits may be linked to a reduction in ischemia-induced apoptosis and a stimulation of ischemia-induced angiogenesis and neurogenesis. These findings raise perspectives for the use of ECFCs as a well-characterized cell therapy product for optimal therapeutic outcome after stroke.

Keywords

Stroke Late endothelial progenitors Angiogenesis Apoptosis 

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Chahrazad Moubarik
    • 1
  • Benjamin Guillet
    • 1
    • 5
  • Bennis Youssef
    • 1
  • Jean-Laurent Codaccioni
    • 2
  • Marie-Dominique Piercecchi
    • 1
  • Florence Sabatier
    • 1
    • 3
  • Pellegrini Lionel
    • 2
  • Laetitia Dou
    • 1
  • Alexandrine Foucault-Bertaud
    • 1
  • Lionel Velly
    • 2
  • Françoise Dignat-George
    • 1
    • 4
  • Pascale Pisano
    • 1
  1. 1.INSERM UMR 608, Université de la MéditerranéeFaculté de PharmacieMarseilleFrance
  2. 2.Département d’Anesthésie/RéanimationCHU TimoneMarseilleFrance
  3. 3.Laboratoire de Culture et Thérapie Cellulaire, INSERM CIC-BT 510CHU ConceptionMarseilleFrance
  4. 4.Département d’HématologieCHU ConceptionMarseilleFrance
  5. 5.INSERM UMR 608, Laboratoire de PharmacodynamieFaculté de PharmacieMarseilleFrance