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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
doi: https://doi.org/10.1101/2022.10.04.510637
Giulia Coppiello
1Program 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
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  • For correspondence: xlaranguren@unav.es gcoppiello@unav.es
Paula Barlabé
1Program 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
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Marta Moya-Jódar
1Program 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
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Gloria Abizanda
1Program 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
2Department of Hematology and Cell Therapy, Clínica Universidad de Navarra, Pamplona, 31008, Spain
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Carolina Barreda
1Program 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
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Elena Iglesias
1Program 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
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Javier Linares
3Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307 Dresden, Germany
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Estibaliz Arellano-Viera
4Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany
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Adrian Ruiz-Villalba
5Department of Animal Biology, University of Málaga, Málaga, 29010, Spain; Andalusian Centre for Nanomedicine and Biotechnology (BIONAND)-Biomedical Research Institute of Malaga (IBIMA), Málaga, 29590, Spain
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Eduardo Larequi
1Program 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
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Xonia Carvajal-Vergara
1Program 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
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Beatriz Pelacho
1Program 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
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Felipe Prósper
1Program 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
2Department of Hematology and Cell Therapy, Clínica Universidad de Navarra, Pamplona, 31008, Spain
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Xabier L. Aranguren
1Program 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
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  • For correspondence: xlaranguren@unav.es gcoppiello@unav.es
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SUMMARY

The generation of organs from stem cells by blastocyst complementation is a promising approach to cover 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 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.

Competing Interest Statement

The authors have declared no competing interest.

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Posted October 04, 2022.
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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
bioRxiv 2022.10.04.510637; doi: https://doi.org/10.1101/2022.10.04.510637
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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
bioRxiv 2022.10.04.510637; doi: https://doi.org/10.1101/2022.10.04.510637

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