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Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization
Cardiovascular, Renal and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Mölndal, Sweden.
Cardiovascular, Renal and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Mölndal, Sweden.
Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Discovery Sciences, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Mölndal, Sweden. (Bioinformatik, Bioinformatics)
Discovery Sciences, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Mölndal, Sweden.
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2018 (Engelska)Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 7458Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

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Nature Publishing Group, 2018. Vol. 8, artikel-id 7458
Nationell ämneskategori
Cellbiologi
Forskningsämne
Bioinformatik; INF502 Biomarkörer
Identifikatorer
URN: urn:nbn:se:his:diva-15166DOI: 10.1038/s41598-018-25883-xISI: 000431763100010PubMedID: 29748585Scopus ID: 2-s2.0-85046939424OAI: oai:DiVA.org:his-15166DiVA, id: diva2:1210031
Projekt
BioMineTillgänglig från: 2018-05-25 Skapad: 2018-05-25 Senast uppdaterad: 2018-11-23Bibliografiskt granskad

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Granéli, Cecilia

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Institutionen för biovetenskapForskningscentrum för Systembiologi
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