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Regeneration of Three Layers Vascular Wall by using BMP2-Treated MSC Involving HIF-1α and Id1 Expressions Through JAK/STAT Pathways

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Summary

Engineering living, multilayered blood vessels to form in vivo arteries is a promising alternative to peripheral artery bypass using acellular grafts restricted by thrombosis and occlusion at long term. Bone Morphogenetic Protein 2 (BMP2) is a growth factor determining in the early vascular embryonic development. The aim of the present study was evaluate the collaborative effect of recombinant human—BMP2 and Bone marrow—Mesenchymal stem cells (BM-MSCs) seeded on vascular patch to regenerate a vascular arterial wall in a rat model. BM-MSCs expressing green fluorescent protein (GFP) seeded on vascular patch were cultured in presence of recombinant human-BMP2 [100 ng/mL] during 1 week before their implantation on the abdominal aorta of Wistar rats. We observed after 2 weeks under physiological arterial flow a regeneration of a three layers adult-like arterial wall with a middle layer expressing smooth muscle proteins and a border layer expressing endothelial marker. In vitro study, using Matrigel assay and co-culture of BM-MSCs with endothelial cells demonstrated that rh-BMP2 promoted tube-like formation even at long term (90 days) allowing the organization of thick rails. We demonstrated using inhibitors and siRNAs that rh-BMP2 enhanced the expression of HIF-1α and Id1 through, at least in part, the stimulation of JAK2/STAT3/STAT5 signaling pathways. Rh-BMP2 by mimicking embryological conditions allowed vascular BM-MSCs differentiation.

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The authors declare no potential conflicts of interest.

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Authors and Affiliations

  1. Faculty of Medicine, University François Rabelais, Labpart EA 3852, IFR 135, Tours, France

    Karim Belmokhtar, Thierry Bourguignon, Morel E. Worou, Georges Khamis, Pierre Bonnet & Véronique Eder

  2. Microenvironment of Hematopoiesis and Stem Cells, Faculty of Medicine, University François Rabelais, EA 3855, IFR 135, Tours, France

    Jorge Domenech

Authors
  1. Karim Belmokhtar
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  2. Thierry Bourguignon
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  3. Morel E. Worou
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  4. Georges Khamis
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  7. Véronique Eder
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Correspondence to Karim Belmokhtar.

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Belmokhtar, K., Bourguignon, T., Worou, M.E. et al. Regeneration of Three Layers Vascular Wall by using BMP2-Treated MSC Involving HIF-1α and Id1 Expressions Through JAK/STAT Pathways. Stem Cell Rev and Rep 7, 847–859 (2011). https://doi.org/10.1007/s12015-011-9254-6

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