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Nestin is a New Partner in Endothelial Colony Forming Cell Angiogenic Potential

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Abstract

Nestin, an intermediate filament protein expressed by progenitor cells, is associated with tissue regeneration. Although nestin expression has been reported in poorly differentiated and newly formed blood vessels, its role in endothelial cells remains unclear. In this study, we investigated the involvement of nestin in the angiogenic properties of endothelial colony-forming cells (ECFCs) derived from human umbilical cord blood. Our results demonstrate that ECFCs express high levels of nestin, and that its inhibition by small interfering RNAs decreased ECFC proliferation, migration in response to SDF-1 and VEGF-A, tubulogenesis, and adhesion on collagen. These effects are associated with modulation of focal adhesion kinase phosphorylation. Furthermore, nestin silencing resulted in reduced revascularization in a mouse hindlimb ischemia model. In conclusion, these findings provide evidence that nestin more than being a structural protein, is an active player in ECFC angiogenic properties.

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Data Availability

Raw data are available upon request.

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Funding

This work was supported by AP-HP, Université de Paris Cité and Inserm.

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Authors and Affiliations

  1. Université de Paris Cité, INSERM, Innovative Therapies in Hemostasis, F-75006, Paris, France

    Audrey Cras, Elisa Rossi, Adeline Blandinières, Pascale Gaussem & David M. Smadja

  2. Cell therapy unit, AP-HP, Saint Louis Hospital, F-75010, Paris, France

    Audrey Cras & Jérôme Larghero

  3. Université de Paris Cité, INSERM, U976, CIC-BT, F-75010, Paris, France

    Jérôme Larghero

  4. Hematology department, AP-HP, Georges Pompidou European Hospital, F-75015, Paris, France

    Adeline Blandinières, Pascale Gaussem & David M. Smadja

  5. Inserm Innovative Therapies in Haemostasis, 56 rue Leblanc, F-75015, Paris, France

    David M. Smadja

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  1. Audrey Cras
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  2. Jérôme Larghero
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Contributions

AC and DMS designed the study and wrote the paper. AC, ER and AB performed the experiments and analyzed data. AC, JL, PG and DMS interpreted and discussed results. Authors declare that the submitted work is original and has not been published before (neither in English nor in any other language) and that the work is not under consideration for publication elsewhere.

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Correspondence to David M. Smadja.

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Human umbilical cord blood were provided by Saint-Louis Hospital Biological Resources Center - Cord Blood Bank after information and consent of mothers, under French Health Ministry authorization (n°AC-2016-2759).

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Cras, A., Larghero, J., Rossi, E. et al. Nestin is a New Partner in Endothelial Colony Forming Cell Angiogenic Potential. Stem Cell Rev and Rep 19, 2541–2550 (2023). https://doi.org/10.1007/s12015-023-10587-1

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