Chemotherapy Induced Cardiotoxicity Analysis of Oxaliplatin on Human Heart Organoids Using Optical Coherence Tomography AHA Conference Repository

American Heart Association

141

Final ID: LBP5

Chemotherapy Induced Cardiotoxicity Analysis of Oxaliplatin on Human Heart Organoids Using Optical Coherence Tomography

Abstract Body (Do not enter title and authors here): Oxaliplatin, a platinum based cytotoxic drug has been the standard treatment for advanced colorectal cancer. One of its least investigated side effects include cardiotoxicity as it causes rapid breathing, arrhythmia and tachycardia in various clinical cases. Human heart organoids (hHOs) are three-dimensional (3D) miniature hearts developed from human induced pluripotent stem cells (hiPSCs). They have phenomenal capabilities to recapitulate cardiac physiology that could help overcome the limitations of the current cardiotoxicity models. Optical coherence tomography (OCT) is a non-invasive and label-free imaging that can effectively characterise an organoid's 3D morphological features throughout the experimental period. This study aims to postulate an in-situ cardiotoxicity analysis model to determine cardiotoxic effects of oxaliplatin on human heart organoids.The morphological and physiological parameters are characterised using customised Spectral Domain Optical Coherence Tomography (SD-OCT) and calcium imaging. Wild-type C hiPSCs expressing calcium indicator GCaMP6f, were used to fabricate hHOs. After 20 days of organoid development, hHOs were exposed to various concentrations of oxaliplatin. The imaging setup provides an in situ model that enables imaging of organoids within the cell culture environment of the incubator. Oxaliplatin at higher concentrations (70-100µM) was observed to induce a rapid 76.9% increase in organoid’s beats per minute after one day of exposure which could be attributed to tachycardia effects observed in clinical cases. However, these organoids had a drastic decline of beats per minute and eventually ceased to beat by day 4. The beating intensity of organoids exposed to higher oxaliplatin doses reduced over time along with a decrease in relaxation and contraction time. Segmentation and 3D rendering using OCT indicate the deterioration of organoid cavities and structural deformation after oxaliplatin exposure that could be linked to decreased contractile functions. Results from this study indicate the efficiency of a combined in situ model for cardiotoxicity analysis using human heart organoids, OCT and calcium imaging modality. After exposure to the drug, organoids rapidly indicate morphological and beating changes that help to recapitulate the 3D tissue level effects of chemotherapy induced cardiotoxicity within a week. A cardiotoxicity model as proposed by this study is essential to be done before clinical application of drugs.

Jose, Joven ( Southeastern University , Bartow , Florida , United States )
Paul, Ratul ( Washington University in St. Louis , Saint Louis , Missouri , United States )
Wang, Fei ( Washington University in St. Louis , Saint Louis , Missouri , United States )
Du, Junwei ( Washington University in St. Louis , Saint Louis , Missouri , United States )
Berezin, Mikhail ( Washington University in St. Louis , Saint Louis , Missouri , United States )
Zhou, Chao ( Washington University in St. Louis , Saint Louis , Missouri , United States )

Author Disclosures:

Joven Jose:

DO NOT have relevant financial relationships

Ratul Paul:

No Answer

Fei Wang:

DO NOT have relevant financial relationships

Junwei Du:

No Answer

Mikhail Berezin:

No Answer

Chao Zhou:

No Answer

Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Late-Breaking Basic Science: New Insights in Cardiovascular Health and Disease

Saturday, 11/16/2024 , 10:30AM - 11:30AM

Abstract Poster Session

American Heart Association

Chemotherapy Induced Cardiotoxicity Analysis of Oxaliplatin on Human Heart Organoids Using Optical Coherence Tomography

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