TY - JOUR
T1 - Epicardial slices
T2 - an innovative 3D organotypic model to study epicardial cell physiology and activation
AU - Maselli, D.
AU - Matos, R. S.
AU - Johnson, R. D.
AU - Chiappini, C.
AU - Camelliti, P.
AU - Campagnolo, P.
N1 - Funding Information:
We thank Drs L Dixton, A Reis, and M Henstock from the Pirbright Institute (Pirbright, UK) and the personnel at Newman Abattoir (Farnborough, UK) for their support in procuring the animal tissues. Prof John McVey and the Department of Biochemical Sciences at the University of Surrey, especially the technical team, for their continuing support. This work was supported by the National Centre for the Replacement, Refinement & Reduction of Animals in Research (grant numbers: NC/R001006/1 and NC/ T001216/1). R.S.M. is supported by the Doctoral College studentship award (University of Surrey), R.D.J. by the British Heart Foundation (grant number: FS/17/33/32931), and C.C. by the European Research Council (grant reference: StG EnBioN 759577).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - The epicardium constitutes an untapped reservoir for cardiac regeneration. Upon heart injury, the adult epicardium re-activates, leading to epithelial-to-mesenchymal transition (EMT), migration, and differentiation. While interesting mechanistic and therapeutic findings arose from lower vertebrates and rodent models, the introduction of an experimental system representative of large mammals would undoubtedly facilitate translational advancements. Here, we apply innovative protocols to obtain living 3D organotypic epicardial slices from porcine hearts, encompassing the epicardial/myocardial interface. In culture, our slices preserve the in vivo architecture and functionality, presenting a continuous epicardium overlaying a healthy and connected myocardium. Upon thymosin β4 treatment of the slices, the epicardial cells become activated, upregulating epicardial and EMT genes, resulting in epicardial cell mobilization and differentiation into epicardial-derived mesenchymal cells. Our 3D organotypic model enables to investigate the reparative potential of the adult epicardium, offering an advanced tool to explore ex vivo the complex 3D interactions occurring within the native heart environment.
AB - The epicardium constitutes an untapped reservoir for cardiac regeneration. Upon heart injury, the adult epicardium re-activates, leading to epithelial-to-mesenchymal transition (EMT), migration, and differentiation. While interesting mechanistic and therapeutic findings arose from lower vertebrates and rodent models, the introduction of an experimental system representative of large mammals would undoubtedly facilitate translational advancements. Here, we apply innovative protocols to obtain living 3D organotypic epicardial slices from porcine hearts, encompassing the epicardial/myocardial interface. In culture, our slices preserve the in vivo architecture and functionality, presenting a continuous epicardium overlaying a healthy and connected myocardium. Upon thymosin β4 treatment of the slices, the epicardial cells become activated, upregulating epicardial and EMT genes, resulting in epicardial cell mobilization and differentiation into epicardial-derived mesenchymal cells. Our 3D organotypic model enables to investigate the reparative potential of the adult epicardium, offering an advanced tool to explore ex vivo the complex 3D interactions occurring within the native heart environment.
UR - http://www.scopus.com/inward/record.url?scp=85123184471&partnerID=8YFLogxK
U2 - 10.1038/s41536-021-00202-7
DO - 10.1038/s41536-021-00202-7
M3 - Article
AN - SCOPUS:85123184471
SN - 2057-3995
VL - 7
JO - NPJ Regenerative Medicine
JF - NPJ Regenerative Medicine
IS - 1
M1 - 7
ER -