3D culturing of human pluripotent stem cells-derived endothelial cells for vascular regeneration

人类多能干细胞衍生的内皮细胞的三维培养用于血管再生

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作者:Edit Gara, Eleonora Zucchelli, Annamária Nemes, Zoltán Jakus, Kitti Ajtay, Éva Kemecsei, Gábor Kiszler, Nikolett Hegedűs, Krisztián Szigeti, Iván Földes, Kristóf Árvai, János Kósa, Kraszimir Kolev, Erzsébet Komorowicz, Parasuraman Padmanabhan, Pál Maurovich-Horvat, Edit Dósa, György Várady, Miklós P

Conclusions

A combination of hPSC-EC and biomatrices may be a promising approach to repair ischemic tissues.

Methods

Here, we studied the role of three-dimensional culture on their characteristics and function both in vitro and in vivo.

Results

We found that differentiated hPSC-EC can re-populate decellularized biomatrices; they remain viable, undergo maturation and arterial/venous specification. Human PSC-EC develop antifibrotic, vasoactive and anti-inflammatory properties during recellularization. In vivo, a robust increase in perfusion was detected at the engraftment sites after subcutaneous implantation of an hPSC-EC-laden hydrogel in rats. Histology confirmed survival and formation of capillary-like structures, suggesting the incorporation of hPSC-EC into host microvasculature. In a canine model, hiPSC-EC-seeded onto decellularised vascular segments were functional as aortic grafts. Similarly, we showed the retention and maturation of hiPSC-EC and dynamic remodelling of the vessel wall with good maintenance of vascular patency. Conclusions: A combination of hPSC-EC and biomatrices may be a promising approach to repair ischemic tissues.

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