Biology subjects

Hibino, N.

Publications and source records attributed to Hibino, N..

3 recordsLinked to original sources

bioRxiv2022

Perfusable Apparatus For Thick-tissue Creation And Growth (patch) Of Cardiac Tissue

Cardiac tissue engineering has been developed as a potential alternative treatment for heart failure. However, current 3D tissues are limited in size and thickness due to the lack of an effective vascularization method. We have developed a novel bioreactor system to create viable vascularized cardiac tissue from multicellular spheroids using a digital light processing (DLP) 3D bioprinting system. Spheroids were created from induced pluripotent stem cells (iPSC) and cardiac fibroblasts (FB) using special dimple plates for mass production. One centimeter cubic tissues were created from spheroids using a DLP 3D printed mold with vascular channels. The tissue was maintained in a perfusion chamber under regulated flow and pressure following differentiation to cardiac tissue and endothelialization. Mass production of large spheroids (35,000 / tissue, diameter of 395.99 um +/- 101.15 um) was achieved from 170 million iPSCs and 50 million FBs for the creation of 1cm3 cardiac tissue in a 3D printed mold with vascular channels. The cardiac tissues (n=5) were perfused for 20 days under stable pressure of 17.5 +/- 3.05 PSI and flow of 5000 uL/min +/- 1116.42 uL/min. On days 10 and 20, Alamar blue assays showed viability for all five tissues (Alamar blue intensity: Day 10 1.57 +/- 0.15. Day 20 2.21 +/- 0.19). Thick and viable cardiac tissues were created and maintained using a 3D printed vascularized mold and perfusion system for maturation and growth in vitro for 30 days. This technology will open new doors for viable in vitro cardiac tissue creation.

bioengineering↗

bioRxiv2021

Computational Fontan Analysis: Preserving accuracy while expediting workflow

BackgroundPost-operative outcomes of the Fontan operation have been linked to graft shape after implantation. Computational fluid dynamics (CFD) simulations are used to explore different surgical options. The objective of this study is to perform a systematic in vitro validation for investigating the accuracy and efficiency of CFD simulation to predict Fontan hemodynamics. MethodsCFD simulations were performed to measure indexed power loss (iPL) and hepatic flow distribution (HFD) in 10 patient-specific Fontan models, with varying mesh and numerical solvers. The results were compared with a novel in vitro flow loop setup with 3D printed Fontan models. A high-resolution differential pressure sensor was used to measure the pressure drop for validating iPL predictions. Microparticles with particle filtering system were used to measure HFD. The computational time was measured for a representative Fontan model with different mesh sizes and numerical solvers. ResultsWhen compared to in vitro setup, variations in CFD mesh sizes had significant effect on HFD (p = 0.0002) but no significant impact on iPL (p = 0.069). Numerical solvers had no significant impact in both iPL (p = 0.50) and HFD (P = 0.55). A transient solver with 0.5 mm mesh size requires computational time 100 times more than a steady solver with 2.5 mm mesh size to generate similar results. ConclusionsThe predictive value of CFD for Fontan planning can be validated against an in vitro flow loop. The prediction accuracy can be affected by the mesh size, model shape complexity and flow competition.

bioinformatics↗

bioRxiv2021

Noncanonical Notch signals have opposing roles during cardiac development

The Notch pathway is an ancient intercellular signaling system with crucial roles in numerous cell-fate decision processes across species. While the canonical pathway is activated by ligand-induced cleavage and nuclear localization of membrane-bound Notch, Notch can also exert its activity in a ligand/transcription-independent fashion, which is conserved in Drosophila, Xenopus, and mammals. However, the noncanonical role remains poorly understood in in vivo processes. Here we show that increased levels of the Notch intracellular domain (NICD) in the early mesoderm inhibit heart development, potentially through impaired induction of the second heart field (SHF), independently of the transcriptional effector RBP-J. Similarly, inhibiting Notch cleavage, shown to increase noncanonical Notch activity, suppressed SHF induction in embryonic stem cell (ESC)-derived mesodermal cells. In contrast, NICD overexpression in late cardiac progenitor cells lacking RBP-J resulted in an increase in heart size. Our study suggests that noncanonical Notch signaling has stagespecific roles during cardiac development.

developmental biology↗