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

Scientific Reports
Duong T NguyenSepideh Heydarkhan-Hagvall

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 ...Continue Reading

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Citations

Aug 27, 2019·Frontiers in Cell and Developmental Biology·Amanda LeitolisMarco A Stimamiglio
Aug 14, 2019·Advanced Healthcare Materials·Ziyu WangAnthony S Weiss
Oct 31, 2020·Frontiers in Bioengineering and Biotechnology·Tadeu Ériton Caliman ZanardoBreno Valentim Nogueira
Oct 15, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jie LiaoXiaoming Li
Aug 22, 2021·Stem Cells·Kim OlesenKarl-Henrik Grinnemo

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Software Mentioned

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Proteome Discoverer
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