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

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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.

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Acknowledgements

We thank P. Stellmann for technical assistance in the preparation of ECFCs and the Department of Gynecology and Obstetric of St Joseph Hospital in Marseille for collection of cord blood samples.

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Authors and Affiliations

  1. INSERM UMR 608, Université de la Méditerranée, Faculté de Pharmacie, Marseille, France

    Chahrazad Moubarik, Benjamin Guillet, Bennis Youssef, Marie-Dominique Piercecchi, Florence Sabatier, Laetitia Dou, Alexandrine Foucault-Bertaud, Françoise Dignat-George & Pascale Pisano

  2. Département d’Anesthésie/Réanimation, CHU Timone, Marseille, France

    Jean-Laurent Codaccioni, Pellegrini Lionel & Lionel Velly

  3. Laboratoire de Culture et Thérapie Cellulaire, INSERM CIC-BT 510, CHU Conception, Marseille, France

    Florence Sabatier

  4. Département d’Hématologie, CHU Conception, Marseille, France

    Françoise Dignat-George

  5. INSERM UMR 608, Laboratoire de Pharmacodynamie, Faculté de Pharmacie, 27 boulevard Jean Moulin, 13005, Marseille, France

    Benjamin Guillet

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  1. Chahrazad Moubarik
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  2. Benjamin Guillet
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Correspondence to Benjamin Guillet.

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Chahrazad Moubarik and Benjamin Guillet have equally contributed to the study

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Moubarik, C., Guillet, B., Youssef, B. et al. Transplanted Late Outgrowth Endothelial Progenitor Cells as Cell Therapy Product for Stroke. Stem Cell Rev and Rep 7, 208–220 (2011). https://doi.org/10.1007/s12015-010-9157-y

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