OptoDyCE: Automated system for high-throughput all-optical dynamic cardiac electrophysiology

Klimas, Aleksandra; Jia, Yu; Ambrosi, Christina M.; Williams, John C.; Bien, Harold; Entcheva, Emilia

doi:10.1117/12.2212736

Cited by 14 publications

(29 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since successful application of optogenetics depends on production of a photocurrent large enough to trigger depolarization, expression levels can be critical determinants of experimental outcome. A number of viral [18,25,29,[36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] and non-viral methods [9,10,25,29,31,32,48,[54][55][56][57][58][59][60][61][62][63] have been successfully applied to the cardiomyocyte. For in vivo cardiac application tissue tropism with adeno-associated virus (AAV) types 1 or 6 might be preferable to type 9 used in vitro [64].…”

Section: Optogenetic Tools and Their Deliverymentioning

confidence: 99%

“…Limited comparisons are available for the mechanism of gene delivery (spark cell vs. adenovirus) e.g. [25]. Finally, toxicity or efficacy studies using small molecules are relatively recent additions to this landscape, paralleling the conversion from proof of concept work in animal explant material to human stem-cell derivatives from commercial sources.…”

Section: Optogenetic Tools and Their Deliverymentioning

confidence: 99%

“…The unifying theme for this collection of articles is the added value that induced pluripotent stem cell (iPSc) derivatives may deliver in the drug discovery process. Although it is clear from Table 2 that pioneering work in optical control of cardiac tissues has relied on neonatal rat ventricular or atrial myocytes (NRVM or NRAM) or adult whole heart to establish feasibility, the potential cross-over to use human iPSc derivatives as a renewable in vitro cell model of disease [67] in place of these cell types has been demonstrated [25,36,29,42,44,55].…”

Section: Considerations For Ipsc Cardiomyocyte Substratesmentioning

confidence: 99%

See 2 more Smart Citations

Feasibility of Using Adjunctive Optogenetic Technologies in Cardiomyocyte Phenotyping – from the Single Cell to the Whole Heart

Bub

Daniels

2020

CPB

View full text Add to dashboard Cite

In 1791, Galvani established that electricity activated excitable cells. In the two centuries that followed, electrode stimulation of neuronal, skeletal and cardiac muscle became the adjunctive method of choice in experimental, electrophysiological, and clinical arenas. This approach underpins breakthrough technologies like implantable cardiac pacemakers that we currently take for granted. However, the contact dependence, and field stimulation that electrical depolarization delivers brings inherent limitations to the scope and experimental scale that can be achieved. Many of these were not exposed until reliable in vitro stem-cell derived experimental materials, with genotypes of interest, were produced in the numbers needed for multi-well screening platforms (for toxicity or efficacy studies) or the 2D or 3D tissue surrogates required to study propagation of depolarization within multicellular constructs that mimic clinically relevant arrhythmia in the heart or brain. Here the limitations of classical electrode stimulation are discussed. We describe how these are overcome by optogenetic tools which put electrically excitable cells under the control of light. We discuss how this enables studies in cardiac material from the single cell to the whole heart scale. We review the current commercial platforms that incorporate optogenetic stimulation strategies, and summarize the global literature to date on cardiac applications of optogenetics. We show that the advantages of optogenetic stimulation relevant to iPS-CM based screening include independence from contact, elimination of electrical stimulation artefacts in field potential measuring approaches such as the multi-electrode array, and the ability to print re-entrant patterns of depolarization at will on 2D cardiomyocyte monolayers.

show abstract

Section: Optogenetic Tools and Their Deliverymentioning

confidence: 99%

Section: Optogenetic Tools and Their Deliverymentioning

confidence: 99%

Section: Considerations For Ipsc Cardiomyocyte Substratesmentioning

confidence: 99%

See 1 more Smart Citation

Feasibility of Using Adjunctive Optogenetic Technologies in Cardiomyocyte Phenotyping – from the Single Cell to the Whole Heart

Bub

Daniels

2020

CPB

View full text Add to dashboard Cite

show abstract

“…action potentials (AP), Ca 2+ transients (CaTr), or contraction. Recently, all-optical highthroughput systems allowed simultaneous AP and CaTr measurements from cardiomyocytes within multicellular context, offering means to speed up in vitro drug tests [1,2]. In this work, we aim (i) to calibrate/optimize populations of in silico models of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) by means of simultaneous optically recorded data of APs and CaTrs in control conditions and (ii) to assess the predictive power of our in silico populations during the administration of three specific drugs (Diltiazem, Cisapride and Astemizole) plus a fourth drug (Dofetilide) as positive control.…”

Section: Introductionmentioning

confidence: 99%

In Silico Populations Optimized on Optogenetic Recordings Predict Drug Effects in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Paci

Passini

Klimas

et al. 2018

2018 Computing in Cardiology Conference (CinC)

Self Cite

View full text Add to dashboard Cite

All-optical high-throughput systems allow simultaneous high resolution action potential (AP) and Ca 2+ transient (CaTr) measurements from cardiomyocytes within multicellular context, offering means to speed up in vitro drug tests. Here, we aim to develop experimentallyconstrained in silico models of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and hiPSC-CM populations to predict drug effects in humans, by leveraging functional data obtained by all-optical means. Using multi-objective genetic algorithms (MoGAs), we constructed three control populations of in silico hiPSC-CMs, constrained with experimental data of APs and CaTrs recorded at room temperature and non-paced conditions from three different plates containing hiPSC-CM syncytia. We then simulated the effect of increasing doses of Diltiazem (130 models), Cisapride (200 models) and Astemizole (200 models) in the three populations, respectively. Comparing model predictions with the experimental drug administration (not used for the optimization/calibration of the populations) revealed good agreement with experiments: e.g. Diltiazem shortened APs while Astemizole and Cisapride prolonged APs.

show abstract

“…Beyond optical pacing and defibrillation, optogenetic actuators and fluorescent sensors have been applied to analyse the electrophysiological characteristics of patient-derived cells and their specific drug responses [30][31][32]. To do so, primary cardiomyocytes or human stem cell derived cardiomyocytes were virally transduced to express spectrally separated ChRs, Ca 2+ and voltage reporter proteins.…”

Section: Introductionmentioning

confidence: 99%

The power of optogenetics

Schneider-Warme

2018

Herzschr Elektrophys

View full text Add to dashboard Cite

Optogenetics is an emerging, interdisciplinary research area which combines genetic and optical technologies to steer and monitor specific biological processes. To this end, light-activated proteins, so-called optogenetic actuators, or fluorescent sensor proteins are genetically targeted to the cells of interest. Light activation can then be used to modulate or record cellular behaviour with high spatiotemporal precision. In cardiac research, optogenetic approaches have been used to unravel heterocellular electrotonic interactions, both in vitro and in situ. Pioneering optogenetic studies with potential relevance for clinical electrophysiology include light-controlled pacing experiments and optical defibrillation studies. However, despite successful implementation in mouse models, clinical applications are not feasible to date; these will require major advances in gene therapy and in optical techniques.

show abstract

OptoDyCE: Automated system for high-throughput all-optical dynamic cardiac electrophysiology

Cited by 14 publications

References 29 publications

Feasibility of Using Adjunctive Optogenetic Technologies in Cardiomyocyte Phenotyping – from the Single Cell to the Whole Heart

Feasibility of Using Adjunctive Optogenetic Technologies in Cardiomyocyte Phenotyping – from the Single Cell to the Whole Heart

In Silico Populations Optimized on Optogenetic Recordings Predict Drug Effects in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

The power of optogenetics

Contact Info

Product

Resources

About