P095
Generation of heart and vascular system from pluripotent stem cells by blastocyst complementation.
P Barlabé(1,5) G Coppiello(1,5) M Moya-Jódar(1) C Pogontke(2) G Abizanda(1) C Barreda(1) E Iglesias(1) J Linares(3) E Arellano-Viera(4) E Larequi(1) X Carvajal-Vergara(1) B Pelacho(1) MM Mazo(1) A Ullate(1) J M Pérez-Pomares(2) A Ruiz-Villalba(2) F Prósper(1) X L Aranguren(1)
1:Program of Regenerative Medicine, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, 31008, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, 31008, Spain.; 2:Department of Animal Biology, University of Málaga, Málaga, 29010, Spain; IBIMA-Plataforma BIONAND, Málaga, 29590, Spain; 3:Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307 Dresden, Germany.; 4:Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany; 5:these authors contributed equally
Blastocyst complementation is a promising approach to grow functional organs from pluripotent stem cells (PSCs) and solve the worldwide shortage of donor organs for transplant. As endothelial cells play a key role in graft rejection, complementation of both parenchymal and vascular cells is needed to generate rejection-free organs. Here we used the lineage-specific expression of diphtheria toxin subunit A (DTA) driven by Nkx2.5 and Tie2 promoters as a 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 showed normal cardiac function and no signs of histopathological defects in the heart, being able to reach adult stage. Furthermore, we rescued heart formation in an interspecies setting by implementing the cell ablation system for rat-to-mouse blastocyst complementation, obtaining hearts composed completely by rat cardiomyocytes. These findings represent a significant step towards the in vivo generation of transplantable organs.