Scientific publications
Generation of heart and vascular system in rodents by blastocyst complementation
Giulia Coppiello 1 , Paula Barlabé 2 , Marta Moya-Jódar 2 , Gloria Abizanda 3 , Cristina Pogontke 4 , Carolina Barreda 2 , Elena Iglesias 2 , Javier Linares 5 , Estibaliz Arellano-Viera 6 , Eduardo Larequi 2 , Patxi San Martín-Úriz 2 , Xonia Carvajal-Vergara 2 , Beatriz Pelacho 2 , Manuel Maria Mazo 3 , José Maria Pérez-Pomares 4 , Adrián Ruiz-Villalba 4 , Asier Ullate-Agote 2 , Felipe Prósper 7 , Xabier L Aranguren 8
Abstract
Generating organs from stem cells through blastocyst complementation is a promising approach to meet the clinical need for transplants. In order 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 system development separately and in combination, obtaining complemented hearts with cardiomyocytes and endothelial cells of exogenous origin.
Complemented chimeras were viable and reached 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.
CITATION Dev Cell. 2023 Nov 13:S1534-5807(23)00552-X. doi: 10.1016/j.devcel.2023.10.008
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