Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization

Abstract Despite improvements in pre-clinical drug testing models, predictability of clinical outcomes continues to be inadequate and costly due to poor evidence of drug metabolism. Humanized miniature organs integrating decellularized rodent organs with tissue specific cells are translational model...

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Autores principales: Duong T. Nguyen, Matthew O’Hara, Cecilia Graneli, Ryan Hicks, Tasso Miliotis, Ann-Christin Nyström, Sara Hansson, Pia Davidsson, Li-Ming Gan, Maria Chiara Magnone, Magnus Althage, Sepideh Heydarkhan-Hagvall
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Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/4df7ae2b4a4f4e15a84d4f112a0c0c0b
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spelling oai:doaj.org-article:4df7ae2b4a4f4e15a84d4f112a0c0c0b2021-12-02T11:40:54ZHumanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization10.1038/s41598-018-25883-x2045-2322https://doaj.org/article/4df7ae2b4a4f4e15a84d4f112a0c0c0b2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25883-xhttps://doaj.org/toc/2045-2322Abstract Despite improvements in pre-clinical drug testing models, predictability of clinical outcomes continues to be inadequate and costly due to poor evidence of drug metabolism. Humanized miniature organs integrating decellularized rodent organs with tissue specific cells are translational models that can provide further physiological understanding and evidence. Here, we evaluated 4-Flow cannulated rat hearts as the fundamental humanized organ model for cardiovascular drug validation. Results show clearance of cellular components in all chambers in 4-Flow hearts with efficient perfusion into both coronary arteries and cardiac veins. Furthermore, material characterization depicts preserved organization and content of important matrix proteins such as collagens, laminin, and elastin. With access to the complete vascular network, different human cell types were delivered to show spatial distribution and integration into the matrix under perfusion for up to three weeks. The feature of 4-Flow cannulation is the preservation of whole heart conformity enabling ventricular pacing via the pulmonary vein as demonstrated by noninvasive monitoring with fluid pressure and ultrasound imaging. Consequently, 4-Flow hearts surmounting organ mimicry challenges with intact complexity in vasculature and mechanical compliance of the whole organ providing an ideal platform for improving pre-clinical drug validation in addition to understanding cardiovascular diseases.Duong T. NguyenMatthew O’HaraCecilia GraneliRyan HicksTasso MiliotisAnn-Christin NyströmSara HanssonPia DavidssonLi-Ming GanMaria Chiara MagnoneMagnus AlthageSepideh Heydarkhan-HagvallNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Duong T. Nguyen
Matthew O’Hara
Cecilia Graneli
Ryan Hicks
Tasso Miliotis
Ann-Christin Nyström
Sara Hansson
Pia Davidsson
Li-Ming Gan
Maria Chiara Magnone
Magnus Althage
Sepideh Heydarkhan-Hagvall
Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization
description Abstract Despite improvements in pre-clinical drug testing models, predictability of clinical outcomes continues to be inadequate and costly due to poor evidence of drug metabolism. Humanized miniature organs integrating decellularized rodent organs with tissue specific cells are translational models that can provide further physiological understanding and evidence. Here, we evaluated 4-Flow cannulated rat hearts as the fundamental humanized organ model for cardiovascular drug validation. Results show clearance of cellular components in all chambers in 4-Flow hearts with efficient perfusion into both coronary arteries and cardiac veins. Furthermore, material characterization depicts preserved organization and content of important matrix proteins such as collagens, laminin, and elastin. With access to the complete vascular network, different human cell types were delivered to show spatial distribution and integration into the matrix under perfusion for up to three weeks. The feature of 4-Flow cannulation is the preservation of whole heart conformity enabling ventricular pacing via the pulmonary vein as demonstrated by noninvasive monitoring with fluid pressure and ultrasound imaging. Consequently, 4-Flow hearts surmounting organ mimicry challenges with intact complexity in vasculature and mechanical compliance of the whole organ providing an ideal platform for improving pre-clinical drug validation in addition to understanding cardiovascular diseases.
format article
author Duong T. Nguyen
Matthew O’Hara
Cecilia Graneli
Ryan Hicks
Tasso Miliotis
Ann-Christin Nyström
Sara Hansson
Pia Davidsson
Li-Ming Gan
Maria Chiara Magnone
Magnus Althage
Sepideh Heydarkhan-Hagvall
author_facet Duong T. Nguyen
Matthew O’Hara
Cecilia Graneli
Ryan Hicks
Tasso Miliotis
Ann-Christin Nyström
Sara Hansson
Pia Davidsson
Li-Ming Gan
Maria Chiara Magnone
Magnus Althage
Sepideh Heydarkhan-Hagvall
author_sort Duong T. Nguyen
title Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization
title_short Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization
title_full Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization
title_fullStr Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization
title_full_unstemmed Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization
title_sort humanizing miniature hearts through 4-flow cannulation perfusion decellularization and recellularization
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/4df7ae2b4a4f4e15a84d4f112a0c0c0b
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