In vivo generation of heart and vascular system by blastocyst complementation
Giulia Coppiello, Paula Barlabé, Marta Moya-Jódar, Gloria Abizanda, Carolina Barreda, Elena Iglesias, Javier Linares, Estibaliz Arellano-Viera, Adrian Ruiz-Villalba, Eduardo Larequi, Xonia Carvajal-Vergara, Beatriz Pelacho, Felipe Prósper, Xabier L. Aranguren
The generation of organs from stem cells by blastocyst complementation is a promising approach to cover the clinical need for transplants. To generate rejection-free organs, complementation of both parenchymal and vascular cells must be achieved, as endothelial cells play a key role in graft rejection. Here we used a lineage-specific cell ablation system to produce mouse embryos unable to form both the cardiac and vascular systems.
By mouse intraspecies blastocyst complementation, we rescued heart and vascular development separately and in combination, obtaining complemented hearts with cardiomyocytes and endothelial cells of exogenous origin. Complemented chimeras were viable and reached the adult stage, showing normal cardiac function and no signs of histopathological defects in the heart.
Furthermore, we implemented the cell ablation system for rat-to-mouse blastocyst complementation, obtaining xenogeneic hearts whose cardiomyocytes were completely of rat origin. These results represent an advance in the experimentation towards the in vivo generation of transplantable organs.
CITA DEL ARTÍCULO bioRxiv 2022.10.04.510637; doi: https://doi.org/10.1101/2022.10.04.510637