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

Theranostics. 2022 Jun 6;12(10):4684-4702. doi: 10.7150/thno.69938. eCollection 2022.


Rationale: Human induced pluripotent stem cell-derived endothelial cells can be candidates for engineering therapeutic vascular grafts. 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.

Keywords: angiogenesis tracking; endothelial cells; human pluripotent stem cells; multimodality imaging; tissue-engineered vascular grafts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Vessel Prosthesis
  • Cell Differentiation
  • Dogs
  • Endothelial Cells / metabolism
  • Humans
  • Induced Pluripotent Stem Cells* / metabolism
  • Pluripotent Stem Cells*
  • Rats