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Toll-like receptor 3 regulates cord blood-derived endothelial cell function in vitro and in vivo

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Abstract

Circulating endothelial progenitor cells (cEPC) are capable of homing to neovascularisation sites, in which they proliferate and differentiate into endothelial cells. Transplantation of cEPC-derived cells, in particular those isolated from umbilical cord blood (UCB), has emerged as a promising approach in the treatment of cardio-vascular diseases. After in vivo transplantation, these cells may be exposed to local or systemic inflammation or pathogens, of which they are a common target. Because Toll-like receptors (TLR) are critical in detecting pathogens and in initiating inflammatory responses, we hypothesized that TLR may govern UCB cEPC-derived cells function. While these cells expressed almost all TLR, we found that only TLR3 dramatically impaired cell properties. TLR3 activation inhibited cell proliferation, modified cell cycle entry, impaired the in vitro angiogenic properties and induced pro-inflammatory cytokines production. The anti-angiogenic effect of TLR3 activation was confirmed in vivo in a hind-limb ischemic mice model. Moreover, TLR3 activation consistently leads to an upregulation of miR-29b, -146a and -155 and to a deregulation of cytoskeleton and cell cycle regulator. Hence, TLR3 activation is likely to be a key regulator of cEPC-derived cells properties.

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Acknowledgments

This work was supported by a grant from the Agence Nationale de la Recherche (project “Eurocord Lab” no. ANR-07-RIB-005-02).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. AP-HP, Unité de Thérapie Cellulaire et CIC de Biothérapies, Hôpital Saint Louis, 1 Avenue Claude Vellefaux, 75475, Paris Cedex 10, France

    Aurore Grelier, Audrey Cras, Nicole Balitrand, Hélène Riesterer, Delphine Freida, Jérôme Larghero & Valérie Vanneaux

  2. Université Paris Diderot, Sorbonne Paris Cité, 75475, Paris, France

    Aurore Grelier, Audrey Cras, Nicole Balitrand, Hélène Riesterer, Delphine Freida, Wendy Cuccini, Regis Peffault de Latour, Jérôme Larghero & Valérie Vanneaux

  3. INSERM UMRS940, Institut Universitaire d’Hématologie, Paris, France

    Audrey Cras, Séverine Lecourt, Jérôme Larghero & Valérie Vanneaux

  4. INSERM U972, IFR69, Hôpital Paul Brousse, Villejuif, France

    Catherine Delmau, Jean-Jacques Lataillade, Marie-Caroline Lebousse-Kerdiles & Georges Uzan

  5. Université Paris Descartes, Sorbonne Paris Cité, 75015, Paris, France

    Yves Lepelletier

  6. Unité de Thérapie Cellulaire et Tissulaire, CTS des Armées, Hôpital Militaire Percy, BP410, 92141, Clamart Cedex, France

    Jean-Jacques Lataillade

  7. AP-HP, Laboratoire Central d’Hématologie, Hôpital Saint Louis, Paris, France

    Wendy Cuccini

  8. AP-HP, Service d’Hématologie Greffe, Hôpital Saint Louis, Paris, France

    Regis Peffault de Latour

  9. Département d’Hématologie Clinique, Hôpital d’Amiens, Amiens, France

    Jean-Pierre Marolleau

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  1. Aurore Grelier
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  2. Audrey Cras
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  3. Nicole Balitrand
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Correspondence to Valérie Vanneaux.

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Grelier, A., Cras, A., Balitrand, N. et al. Toll-like receptor 3 regulates cord blood-derived endothelial cell function in vitro and in vivo. Angiogenesis 16, 821–836 (2013). https://doi.org/10.1007/s10456-013-9358-5

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  • DOI: https://doi.org/10.1007/s10456-013-9358-5

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