Endothelial Cell Replacement of Human Veins, Modeling Vascular Repair and Endothelial Cell Chimerism

Allogeneic transplant organs are potentially highly immunogeneic. The endothelial cells (EC) located within the vascular system serve as the primary interface between the recipient's immune system and the donor organ, playing a key role in the allo-immune response. In this study, we investigated the potential use of recipient-derived ECs in a vein recellularization model. Here, human iliac veins underwent complete decellularization using a triton X-100 protocol. We demonstrated the feasibility of re-endothelializing acellular blood vessels using either HUVEC or human venous-derived ECs, with this re-endothelization being sustainable for up to 28 days in vitro. The re-endothelialized veins exhibited the restoration of vascular barrier function, along with the restoration of innate immune regulatory capabilities, evident through the facilitation of monocytic cell transmigration and their polarization towards a macrophage phenotype following trans-endothelial extravasation. Finally, we explored whether recellularization with EC of a different donor could prevent antibody-mediated rejection. We demonstrated that in chimeric vessels, allogeneic EC became a target of the humoral anti-donor response after activation of the classical immune complement pathway whereas autologous EC were spared, emphasizing their potential utility prior to transplantation. In conclusion, our study demonstrates that replacement of EC in transplants could reduce the immunological challenges associated with allogeneic grafts.