Automated analysis of human cardiomyocytes dynamics with holographic image-based tracking for cardiotoxicity screening

• This paper proposes a new non-invasive, low-cost, and fully automated platform to quantitatively analyze dynamics of human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) at the single-cell level by holographic image-based tracking for cardiotoxicity screening. A dense Farneback optical flow method and holographic imaging informatics were combined to characterize the contractile motion of a single CM, which obviates the need for costly equipment to monitor a CM's mechanical beat activity. The reliability of the proposed platform was tested by single-cell motion characterization, synchronization analysis, motion speed measurement of fixed CMs versus live CMs, and noise sensitivity. The applicability of the motion characterization method was tested to determine the pharmacological effects of two cardiovascular drugs, isoprenaline (166 nM) and E−4031 (500 μM). The experiments were done using single CMs and multiple cells, and the results were compared to control conditions. Cardiomyocytes responded to isoprenaline by increasing the action potential (AP) speed and shortening the resting period, thus increasing the beat frequency. In the presence of E−4031, the AP speed was decreased, and the resting period was prolonged, thus decreasing the beat frequency. The findings offer insights into single hiPS-CMs’ contractile motion and a deep understanding of their kinetics at the single-cell level for cardiotoxicity screening. 

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

Keyword

Cardiomyocyte characterization

Cardiomyocyte motion tracking

Cardiotoxicity screening

High content screening

Label-free biosensors

Optical imaging

Cytology

Motion analysis

Reliability analysis

Stem cells

Cardiomyocytes

Cardiotoxicity

High-content screening

Holographic images

Image based tracking

Label-free biosensor

Holography

Publication and Content Type

ref (subject category)

art (subject category)