2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
July 3rd, 2025
Version: 1
The George Washington University
bioengineering
biorxiv

Response of human iPSC-cardiomyocytes to adrenergic drugs assessed by high-throughput pericellular oxygen measurements

Li, W.Open in Google Scholar•McLeod, D.Open in Google Scholar•Heinson, Y. W.Open in Google Scholar•Kay, M. W.Open in Google Scholar•Li, Z.Open in Google Scholar•Entcheva, E.Open in Google Scholar

Rate-modulating drugs, such as adrenergic agonists and antagonists, are widely used in the treatment of cardiovascular conditions. Preclinical assessment of new rate and metabolism modulators can be augmented through the development of high-throughput (HT) methods that allow chronic measurements. Such approaches are best coupled with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) - a scalable experimental model of the human heart. Here, we evaluate the utility of long-term optical (label-free) measurements of pericellular oxygen in a HT format (96-well plates) for the assessment of the effectiveness of adrenergic drugs in hiPSC-CMs. Quantitative metrics were derived from these long-term measurements, e.g. steady-state pericellular oxygen and time to reach 5%, and we sought correlation to measurements performed in the same samples using all-optical electrophysiology. Adrenergic agonists significantly increased oxygen consumption rate, and this was best seen in the kinetics of initial depletion of pericellular oxygen, i.e. time to reach 5%. Adrenergic antagonists decreased oxygen consumption rate and their action was best quantified using steady-state values for pericellular oxygen after at least 5 hours. Drug type identification based on oxygen consumption rate correlated well with the acute measurements of spontaneous rate in the same samples. Furthermore, we showed that direct rate modulation with chronic optogenetic pacing detectably sped up the oxygen consumption rate and optogenetic transformation did not interfere with classification of adrenergic drugs. We conclude that HT label-free optical oxygen measurements may be a valuable approach for long-term non-invasive monitoring of the action of rate- and metabolism-modulating drugs in preclinical studies.

Similar Papers

biorxiv
Sat Jul 05 2025
Focal neurostimulation of propagating calcium waves in human neural cells using megahertz-range single-pulse focused ultrasound
Focused ultrasound (FUS) offers a promising neurostimulation technique that addresses the trade-off between invasiveness and spatial selectivity found in conventional electromagnetic-based methods. Evidence supporting its theoretical selectivity and comprehensive descriptions of the underlying biophysical mechanisms remain insufficient to ensure adequate control and safety. Based on observations o...
Aubier, T.
•
Suarez-Castellanos, I. M.
•
Perier, M.
•
Huberfeld, G.
...•
N'Djin, W. A.
biorxiv
Sat Jul 05 2025
Signal Detection of Point Targets Using Eigen-Images for Super-Resolution Ultrasound Imaging and Gas Vesicle Localization
Accurate signal detection of ultrasound contrast agents, such as microbubble (MB) and gas vesicle (GV), in the presence of clutter and noise is essential to increase image quality in super-resolution ultrasound imaging (SRUS) and achieve precise GV localization. We developed and evaluated an eigen-image based signal detection method using singular value decomposition (SVD) and changepoint detectio...
Bhattacharjee, A.
•
Turner, S.
•
Diao, L.
•
Zhang, S.
•
Yoon, S.
biorxiv
Sat Jul 05 2025
Scale-Specific Viscoelastic Characterization of Hydrogels: Integrated AFM and Finite Element Modeling
Viscoelastic hydrogels mimic the dynamic mechanical properties of native extracellular matrices, making them essential for biomedical applications. However, characterizing their scale-dependent mechanical properties remains challenging, despite their critical influence on cell-material interactions and biomaterial performance. Here, we present an integrated experimental-computational approach to q...
Fertala, N.
•
Uhlmann, K.
•
Grigoryev, E.
•
Seth, P.
...•
Balzani, D.
biorxiv
Sat Jul 05 2025
A Compact Two-Photon Module for Simultaneous Dual-Depth, Multi-Region in vivo Brain Imaging
Understanding how distributed brain regions interact across cortical depths is crucial for uncovering the neural basis of behavior and cognition. Two-photon microscopy (2PM) excels at imaging the superficial layer, while three-photon microscopy (3PM) penetrates deep tissues but lacks sufficient speed for capturing fast superficial dynamics. Here, we present a compact two-photon imaging module (2PI...
Zhao, Y.
•
Gu, X.
•
Kong, C.
•
Liu, S.
...•
Li, B.
biorxiv
Sat Jul 05 2025
Volumetric Bioprinting of Bone-like Mineralizing Hydrogel Constructs in the Presence of High Cell Densities and Mineral Precursors
A major challenge in bone tissue engineering is the embedding of osteocyte-like cells at high density within a mineralized matrix at the micro-scale and a trabecular-like architecture at the macro-scale. Volumetric bioprinting (VBP) enables rapid creation of complex cell-laden constructs through tomographic light projections. However, integrating both high cell densities and inorganic mineral prec...
de Wildt, B. W. M.
•
Bernero, M.
•
Zauchner, D.
•
Mueller, R.
•
Qin, X.-H.
biorxiv
Sat Jul 05 2025
Optical Coherence Tomography with Fluorescein Optical Clearing for Transscleral Image Guidance
Optical coherence tomography (OCT) is a non-invasive, three-dimensional imaging modality demonstrated to yield a wealth of high-resolution structural and functional information in a variety of biomedical imaging applications. However, there is a significant limitation on the penetration depth of the modality in most tissues due to their high optical scattering, hindering imaging of more deeply emb...
Trout, R. M.
•
Narawane, A.
•
Viehland, C.
•
Ownagh, V.
...•
Toth, C.
biorxiv
Sat Jul 05 2025
Phased affinity-controlled delivery of vascular endothelial growth factor, fibroblast growth factor-2, and platelet derived growth factor enhances in vitro angiogenesis
Angiogenesis, the growth of vasculature from existing blood vessels, requires the coordinated secretion of multiple angiogenic growth factors that each stimulate the cellular recruitment, patterning, and morphogenesis inherent to vascular network formation. Among these secreted factors, vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and platelet derived growth facto...
Svendsen, J. E.
•
Asnes, C. L.
•
Nightheart, S. R.
•
Ford, M. R.
...•
Hettiaratchi, M. H.
biorxiv
Sat Jul 05 2025
A combined Eulerian-Lagrangian and thin film approximation model to investigate the disease-specific drug delivery efficacy on realistic lung geometry and breathing profiles
This study presents a computational assessment of antiviral liquid particle deposition in realistic human respiratory airways, comparing the actual inhalation cycle of a chronic obstructive pulmonary disease (COPD) patient to an ideal and healthy subject. Antiviral drugs are inhaled as fine droplets or mist, forming a thin liquid film along the airway walls of critical areas where respiratory viru...
Verma, S. K.
•
Bhardwaj, S.
•
Patel, K. S.
•
Naik, B. K.
biorxiv
Sat Jul 05 2025
Long-acting hydrogel-based depot formulations of tirzepatide and semaglutide for the management of type 2 diabetes and weight
Several incretin hormone therapies have been clinically approved and have revolutionized the treatment of diabetes and obesity. Promising therapeutics include semaglutide (Ozempic and Wegovy), an agonist for glucagon-like peptide-1 (GLP-1) receptor, and tirzepatide (Mounjaro), a dual agonist for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors. These molecules help to regulat...
d'Aquino, A. I.
•
Dong, C.
•
Nguyen, L. T.
•
Yan, J.
...•
Appel, E. A.
biorxiv
Sat Jul 05 2025
Screening of a pooled library of chimeric antigen receptor T cells based on secretory function
Chimeric antigen receptor (CAR) T cell therapies have shown promise in treating hematologic malignancies, but challenges remain due to immune suppression, antigen heterogeneity, and insufficient functional screening platforms. Here, we present a modular nanovial-based platform for high-throughput, single-cell functional screening of pooled CAR T cell libraries. Nanovials, hydrogel microparticles w...
Soemardy, C.
•
Mei, A.
•
Castellanos-Rueda, R.
•
Espinoza, N. G.
...•
Di Carlo, D.