Background

xCELLigence® RTCA CardioECR System

Platform used in the Sheikh lab
Designed to be placed in a standard tissue culture incubator
Simultaneously measures cardiomyocyte contractile & electrical activities in a 48-well plate (E-Plate)
Compatible with induced pluripotent stem (iPS) cell-derived, or primary cardiomyocytes.
Rapid data acquisition rate (2 msec/plate).
E-Plates are advertised as single use and cost $13,820 for a 36 pack ($383.89 each)

A: E-Plate® CardioECR 48 B: Multi-electrode array(MEA) C: Simultaneous recording of impedance and field potential

Cardiovascular Disease and Drug Screening

Cardiac disease causes more than 600,000 deaths in the U.S every year [1]
Global cost of heart failure is nearly $100 billion [2]
28% of all clinical trials fail due to adverse cardiac side effects while 1 in 7 drugs is recalled from market due to off target side effects and cardiotoxicity [2]
Current screening methods use primary neonatal rat cardiomyocytes, tumor cell lines, and embryonic stem cell (ESC) derived cardiomyocytes
A better approach: human induced pluripotent stem cell (hiPSCs) derived cardiomyocytes
Less ethical concerns (derived from fibroblasts)
Can be disease specific

Arrhythmogenic right ventricular cardiomyopathy (ARVC)

ARVC is a rare familial disorder that may cause ventricular tachycardia and sudden cardiac death in young, apparently healthy individuals [3]
ARVC is caused by mutations in genes that encode desmosomal proteins, which are involved with cell-to-cell adhesion. [3]
The Sheikh Lab currently uses hiPSC derived cardiomyocytes to model ARVC
Dr. Sheikh’s focus is electrophysiological measurements because ARVC is characterized by fat deposits and scarring on the heart tissue, and exercise-induced tachycardia
Need for disease model: most people die before being diagnosed; of the 40% of patients who are diagnosed still die 10-11 years later even with therapeutic treatment

Photo sources: ACEA Biosciences
xCELLigence® RTCA CardioECR System Specifications: “xCELLigence RTCA CardioECR System Spec Sheet”. ACEA Biosciences, Inc.https://www.aceabio.com/wp-content/uploads/CardioECR_Spec_Sheet.pdf
[1]: CDC, NCHS. Underlying Cause of Death 1999-2013 on CDC WONDER Online Database, released 2015. Data are from the Multiple Cause of Death Files, 1999-2013, as compiled from data provided by the 57 vital statistics jurisdictions through the Vital Statistics Cooperative Program. Accessed Feb. 3, 2015.
[2]: Denning, Chris et al. “Cardiomyocytes from Human Pluripotent Stem Cells: From Laboratory Curiosity to Industrial Biomedical Platform.” Biochimica et Biophysica Acta 1863.7 Part B (2016): 1728–1748. PMC. Web. 30 Sept. 2018.
[3]: “Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C).” Johns Hopkins Medicine Health Library, www.hopkinsmedicine.org/health/conditions-and-diseases/arrhythmogenic-right-ventricular-dysplasia--cardiomyopathy-arvdc.

Page Leader: Yu Liu

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