Biology subjects

Funakoshi, S.

Publications and source records attributed to Funakoshi, S..

2 recordsLinked to original sources

bioRxiv2023

Modeling cardiac fibroblast heterogeneity from human pluripotent stem cell-derived epicardial cells

Abstract (Summary) Cardiac fibroblasts play an essential role in the development of the heart and have been implicated in disease progression in the context of fibrosis and regeneration. Here, we established a simple organoid culture platform using human pluripotent stem cell-derived epicardial cells and ventricular cardiomyocytes to study cardiac fibroblasts development, maturation and heterogeneity under normal conditions and following treatment with pathological stimuli. We demonstrated that this system models the early interactions between epicardial cells and cardiomyocytes to generate a population of fibroblasts that recapitulates many aspects of fibroblast behaviour in vivo including changes associated with maturation and in response to pathological stimuli associated with cardiac injury. Using single cell transcriptomics, we show that the hPSC-derived organoid fibroblast population displays a high degree of heterogeneity that approximates the heterogeneity of populations in both the normal and diseased human heart. Additionally, we identified a unique subpopulation of fibroblasts possessing reparative features previously characterized in the hearts of model organisms. Taken together, our system recapitulates many aspects of human cardiac fibroblast specification, development and maturation providing a platform to investigate the role of these cells in human cardiovascular development and disease.

cell biology↗

bioRxiv2022

Non-invasive quantification of contractile dynamics in cardiac cells, spheroids and organs-on-a-chip using high frequency ultrasound

Cell-based models that mimic in vivo heart physiology are poised to make significant advances in cardiac disease modeling and drug discovery. In these systems, cardiomyocyte (CM) contractility is an important functional metric, but current measurement methods are inaccurate, low-throughput, or require complex set-ups. To address this need, we developed a standalone non-invasive, label-free ultrasound technique operating at 40-200 MHz to measure the beat rate, beat rhythm, and force of contraction of cardiac models, ranging from single adult CMs to 3D microtissue constructs in standard cell culture formats. The high temporal resolution of 1000 fps resolved the beat profile of single mouse CMs paced at up to 9 Hz, revealing limitations of lower speed optical based measurements to resolve beat kinetics or characterize aberrant beats. Coupling of ultrasound with traction force microscopy enabled the measurement of CM longitudinal modulus and facile estimation of adult mouse CM contractile forces of 2.34 {+/-} 1.40 N, comparable to more complex measurement techniques. Similarly, measurements of beat rate, rhythm, and drug responses of CM spheroid and microtissue models were demonstrated. In conclusion, ultrasound can be used for the rapid characterization of CM contractile function in a wide range of commonly-studied configurations ranging from single cells to 3D tissue constructs using standard well plates, with applications in cardiac drug discovery and cardiotoxicity evaluation.

bioengineering↗