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Fucoidan promotes early step of cardiac differentiation from human embryonic stem cells and long term maintenance of beating areas.

Abstract : Somatic stem cells require specific niches and 3D scaffolds may provide a way to mimic this microenvironment. Here, we tested a scaffold based on fucoidan, a sulfated polysaccharide known to influence morphogen gradients during embryonic development, to support human Embryonic Stem Cells (hESCs) differentiation towards the cardiac lineage. A macroporous (pore 200 µm) Fucoidan scaffold was selected to support hESCs attachment and proliferation. Using a protocol based on the cardiogenic morphogen BMP2 and TGFb followed by TNFa, an effector of cardiopoietic priming. we examined the cardiac differentiation in the scaffold compared to culture dishes and embryoid bodies (EBs). At day 8, Fucoidan scaffolds supported a significantly higher expression of all 3 genes encoding for transcription factors marking the early step of embryonic cardiac differentiation NKX2.5 (p<0.05), MEF2C (p<0.01) and GATA4 (p<0.01), confirmed by flow cytometry analysis for MEF2C and NKX2.5. Fucoidan scaffolds ability to locally concentrate and slowly release TGF and TNF was confirmed by Luminex technology. We also found that Fucoidan scaffolds supported the late stage of embryonic cardiac differentiation marked by a significantly higher ANF expression (p<0.001), although only rare beating areas were observed. We postulated that absence of mechanical stress in the soft hydrogel impaired sarcomere formation, as confirmed by molecular analysis of the cardiac muscle myosin MYH6 and immunohistological staining of sarcomeric -actinin. Nevertheless, Fucoidan scaffolds contributed to the development of thin filaments connecting beating areas through promotion of smooth muscle cells, thus enabling maintenance of beating areas for up to 6 months. In conclusion, Fucoidan scaffolds appear as a very promising biomaterial to control cardiac differentiation from hESCs that could be combined with mechanical stress to promote sarcomere formation at terminal stages of differentiation.
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Submitted on : Tuesday, January 14, 2014 - 10:27:10 AM
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Sofiane Hamidi, Didier Letourneur, Rachida Aid, Antonio Di Stefano, William Vainchenker, et al.. Fucoidan promotes early step of cardiac differentiation from human embryonic stem cells and long term maintenance of beating areas.. Tissue Engineering: Parts A, B, and C, Mary Ann Liebert, 2014, 20 ((7-8)), pp.1285-94. ⟨10.1089/ten.TEA.2013.0149⟩. ⟨inserm-00929926⟩

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